Journal articles: 'Dendritic cells NLRP3'

1

Tzu-Hsuan, Chang, and Wu-Hsieh Betty A. "Inflammasome activation in Histoplasma stimulated-dendritic cells (P3071)." Journal of Immunology 190, no. 1_Supplement (May 1, 2013): 125.13. http://dx.doi.org/10.4049/jimmunol.190.supp.125.13.

Full text

Abstract:

Abstract Histoplasma capsulatum is an opportunistic dimorphic fungal pathogen. Dendritic cells take up Histoplasma yeasts and present antigens to activate both CD4 and CD8 T cells. Therefore, the interaction of dendritic cells with the fungus is critical to host defense against Histoplasma infection. Here, we investigated the mechanism of inflammasome activation in dendritic cells after infection with Histoplasma. Interaction of bone marrow-derived dendritic cells with Histoplasma activated caspase-1 and induced the secretion of IL-1β. Using blocking antibodies we also found that Dectin-2 regulated pro-IL-β gene transcription and caspase-1 activation after Histoplasma infection in dendritic cells. Histoplasma interaction with Dectin-2 triggered both the first (transcription of pro-IL-1β) and the second (activation of caspase-1) signals in response to Histoplasma stimulation. Cells with NLRP3-deficiency failed to activate caspase-1 and to process pro-IL-1β, showing that NLRP3 is an important pattern recognition receptor in the cytosol to control inflammasome activation by Histoplasma. Thus, our results demonstrated that both Dectin-2 and NLRP3 play important roles in inflammasome activation after Histoplasma infection.

APA, Harvard, Vancouver, ISO, and other styles

2

Wei, Meili, Lu Wang, Tao Wu, Jun Xi, Yuze Han, Xingxiang Yang, Ding Zhang, Qiang Fang, and Bikui Tang. "NLRP3 Activation Was Regulated by DNA Methylation Modification duringMycobacterium tuberculosisInfection." BioMed Research International 2016 (2016): 1–10. http://dx.doi.org/10.1155/2016/4323281.

Full text

Abstract:

Mycobacterium tuberculosis(Mtb) infection activates the NLRP3 inflammasome in macrophages and dendritic cells. Much attention has been paid to the mechanisms for regulation of NLRP3 against Mtb. However, whether epigenetic mechanisms participated in NLRP3 activation is still little known. Here we showed that NLRP3 activation was regulated by DNA methylation modification. Mtb infection promoted NLRP3 activation and inflammatory cytokines expression. NLRP3 promoter was cloned and subsequently identified by Dual-Luciferase Reporter System. The results showed that NLRP3 promoter activity was decreased after methylation by DNA methylaseSssIin vitro. Meanwhile, DNA methyltransferases inhibitor DAC could upregulate the expression of NLRP3. Furthermore, promoter region of NLRP3 gene was demethylated after Mtb H37Rv strain infection. These data revealed that DNA methylation was involved in NLRP3 inflammasome activation during Mtb infection and provided a new insight into the relationship between host and pathogens.

APA, Harvard, Vancouver, ISO, and other styles

3

Hirota, Simon A., Aito Ueno, Sarah E. Tulk, Helen M. Becker, L. Patrick Schenck, Mireille S. Potentier, Yan Li, et al. "Exaggerated IL-15 and Altered Expression of foxp3+ Cell-Derived Cytokines Contribute to Enhanced Colitis in Nlrp3−/− Mice." Mediators of Inflammation 2016 (2016): 1–12. http://dx.doi.org/10.1155/2016/5637685.

Full text

Abstract:

The pathogenesis of Crohn’s disease (CD) involves defects in the innate immune system, impairing responses to microbes. Studies have revealed that mutations NLRP3 are associated with CD. We reported previously that Nlrp3−/− mice were more susceptible to colitis and exhibited reduced colonic IL-10 expression. In the current study, we sought to determine how the loss of NLRP3 might be altering the function of regulatory T cells, a major source of IL-10. Colitis was induced in wild-type (WT) and Nlrp3−/− mice by treatment with dextran sulphate sodium (DSS). Lamina propria (LP) cells were assessed by flow cytometry and cytokine expression was assessed. DSS-treated Nlrp3−/− mice exhibited increased numbers of colonic foxp3+ T cells that expressed significantly lower levels of IL-10 but increased IL-17. This was associated with increased expression of colonic IL-15 and increased surface expression of IL-15 on LP dendritic cells. Neutralizing IL-15 in Nlrp3−/− mice attenuated the severity of colitis, decreased the number of colonic foxp3+ cells, and reduced the colonic expression of IL-12p40 and IL-17. These data suggest that the NLRP3 inflammasome can regulate intestinal inflammation through noncanonical mechanisms, providing additional insight as to how NLRP3 variants may contribute to the pathogenesis of CD.

APA, Harvard, Vancouver, ISO, and other styles

4

Wang, Li-xue, Chao Ren, Ren-qi Yao, Yi-nan Luo, Yue Yin, Yao Wu, Ning Dong, Xiao-mei Zhu, and Yong-ming Yao. "Sestrin2 protects against lethal sepsis by suppressing the pyroptosis of dendritic cells." Cellular and Molecular Life Sciences 78, no. 24 (November 6, 2021): 8209–27. http://dx.doi.org/10.1007/s00018-021-03970-z.

Full text

Abstract:

AbstractSepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Sestrin2 (SESN2), a highly evolutionarily conserved protein, is critically involved in the cellular response to various stresses and has been confirmed to maintain the homeostasis of the internal environment. However, the potential effects of SESN2 in regulating dendritic cells (DCs) pyroptosis in the context of sepsis and the related mechanisms are poorly characterized. In this study, we found that SESN2 was capable of decreasing gasdermin D (GSDMD)-dependent pyroptosis of splenic DCs by inhibiting endoplasmic reticulum (ER) stress (ERS)-related nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)-mediated ASC pyroptosome formation and caspase-1 (CASP-1) activation. Furthermore, SESN2 deficiency induced NLRP3/ASC/CASP-1-dependent pyroptosis and the production of proinflammatory cytokines by exacerbating the PERK–ATF4–CHOP signaling pathway, resulting in an increase in the mortality of septic mice, which was reversed by inhibiting ERS. These findings suggest that SESN2 appears to be essential for inhibiting NLRP3 inflammasome hyperactivation, reducing CASP-1-dependent pyroptosis, and improving sepsis outcomes through stabilization of the ER. The present study might have important implications for exploration of novel potential therapeutic targets for the treatment of sepsis complications.

APA, Harvard, Vancouver, ISO, and other styles

5

Porritt, Rebecca A., David Zemmour, Masanori Abe, Shuang Chen, Timothy R. Crother, Kenichi Shimada, Moshe Arditi, and Magali Noval Rivas. "Single-cell and spatial transcriptomics reveal NLRP3 inflammasome-mediated immunestromal interactions during vasculitis and cardiovascular inflammation." Journal of Immunology 206, no. 1_Supplement (May 1, 2021): 95.01. http://dx.doi.org/10.4049/jimmunol.206.supp.95.01.

Full text

Abstract:

Abstract NLRP3 activation and IL-1β production are implicated in Kawasaki Disease (KD) pathogenesis, however a detailed description of molecular networks and cellular subsets involved is lacking. Here, in a murine model of KD vasculitis, we used single-cell RNA sequencing and spatial transcriptomics to characterize the cellular landscape of vascular tissues and observed infiltrations of innate and adaptive immune cells, associated with increased expression of Nlrp3 and Il1b. Monocytes, macrophages and dendritic cells were the main sources of IL-1β, whereas fibroblasts and vascular smooth muscle cells (VSMCs) expressed high levels of IL-1 receptor. Genetic inhibition of IL-1β signaling on VSMCs efficiently attenuated the development of cardiovascular lesions during murine KD. In addition, pharmacological inhibition of NLRP3 prevented the development of cardiovascular inflammation. Our results unravel the cellular diversity involved in IL-1β production and signaling in KD cardiovascular lesions and demonstrate that therapeutic strategies targeting NLRP3 might be beneficial for human KD.

APA, Harvard, Vancouver, ISO, and other styles

6

BALANESCU, Serban, Elena BARBU, Camelia GEORGESCU, and Andreea Catarina POPESCU. "NLRP3 Inflammasome in Cardiovascular Disease: David`s Stone against Goliath?" Romanian Journal of Cardiology 31, no. 3 (September 24, 2021): 517–27. http://dx.doi.org/10.47803/rjc.2021.31.3.517.

Full text

Abstract:

Inflammation is involved in initiation, development and complications of the vast majority of non-communicable diseases. Recent research demonstrated that infl ammation is involved in pathogenesis of all major cardiovascular diseases. Different endogenous factors (LDL, nucleic acid strands, uric acid – collectively called „Damage Associated Molecular Patterns – DAMPs”) activate dedicated receptors („Pattern Recognition Receptors – PRR”) on monocytes, macrophages or dendritic cells responsible for the innate immunologic response. They have a major role in natural defense mechanisms against different pathogens and in normal conditions have a protective role. Among PRRs „NOD-like, leucin rich, pyrin containing (NLRP)” receptors are a 14-member family located in the cytoplasm. One of these is the NLRP3 resulting from nuclear transcription under the infl uence of NF-kB, a second messenger from membrane PRRs to the nucleus. Mostly the same factors responsible for NLRP3 intracellular expression stimulate its oligomerization resulting in a large protein complex, the NLRP3 infl ammasome. This activates caspase-1 responsible for IL-1b and IL-18 production and initiates an inflammatory reaction leading to various pathologic processes, such as atherosclerosis, hypertension, diabetes and heart failure. This is the current story as we know it of the NLRP3 infl ammasome, a small intracellular component that when inappropriately activated may does more harm than good.

APA, Harvard, Vancouver, ISO, and other styles

7

Mao, Liming, Liping Zhang, Hua Li, Wei Chen, Hongbin Wang, Shuxian Wu, Caiqin Guo, et al. "Pathogenic Fungus Microsporum canis Activates the NLRP3 Inflammasome." Infection and Immunity 82, no. 2 (December 9, 2013): 882–92. http://dx.doi.org/10.1128/iai.01097-13.

Full text

Abstract:

ABSTRACTMicrosporum canisis a pathogenic fungus with worldwide distribution that causes tinea capitis in animals and humans.M. canisalso causes invasive infection in immunocompromised patients. To defy pathogenic fungal infection, the host innate immune system is the first line of defense. As an important arm of innate immunity, the inflammasomes are intracellular multiprotein complexes that control the activation of caspase-1, which cleaves proinflammatory cytokine pro-interleukin-1β (IL-1β) into its mature form. To determine whether the inflammasome is involved in the host defense againstM. canisinfection, we challenged human monocytic THP-1 cells and mouse dendritic cells with a clinical strain ofM. canisisolated from patients with tinea capitis. We found thatM. canisinfection triggered rapid secretion of IL-1β from both THP-1 cells and mouse dendritic cells. Moreover, by using gene-specific shRNA and competitive inhibitors, we determined thatM. canis-induced IL-1β secretion was dependent on NLRP3. The pathways proposed for NLRP3 inflammasome activation, namely, cathepsin B activity, K+efflux, and reactive oxygen species production, were all required for the inflammasome activation triggered byM. canis. Meanwhile, Syk, Dectin-1, and Card9 were found to be involved inM. canis-induced IL-1β secretion via regulation of pro-IL-1β transcription. More importantly, our data revealed thatM. canis-induced production of IL-1β was dependent on the NLRP3 inflammasomein vivo. Together, this study unveils that the NLRP3 inflammasome exerts a critical role in host innate immune responses againstM. canisinfection, and our data suggest that diseases that result fromM. canisinfection might be controlled by regulating the activation of inflammasomes.

APA, Harvard, Vancouver, ISO, and other styles

8

Fernandez, Melissa, Elizabeth Miller, Florian Krammer, Benjamin Greenbaum, and Nina Bhardwaj. "Ion efflux and influenza infection trigger NLRP3 inflammasome signaling in human dendritic cell (VIR5P.1148)." Journal of Immunology 194, no. 1_Supplement (May 1, 2015): 148.16. http://dx.doi.org/10.4049/jimmunol.194.supp.148.16.

Full text

Abstract:

Abstract The NLRP3 inflammasome is an essential intracellular mediator of anti-viral immunity. In murine dendritic cells (DCs) this complex responds to a wide array of signals, including ion efflux and influenza A virus (IAV) infection, to activate caspase-1 mediated proteolysis of interleukin (IL)-1β and IL-18 into biologically active cytokines. However, the presence and function of the NLRP3 inflammasome in human DCs in response to various triggers, including viral infection, has not been clearly defined. Here, we delineate the contribution of the NLRP3 inflammasome to the secretion of IL-1β, IL-18, and IL-1α by human DCs. Activation of the NLRP3 inflammasome in human DCs by various synthetic activators resulted in the secretion of bioactive IL-1β, IL-18, and IL-1α, and induction of pyroptotic cell death. Cellular IL-1β release depended on potassium efflux, and the activity of proteins NLRP3 and caspase-1. Similarly, IAV infection of DCs resulted in priming and activation of the NLRP3 inflammasome and secretion of IL-1β and IL-18 in an M2 and NRLP3 dependent manner. The magnitude of priming by IAV varied amongst different strains and inversely corresponded to type I IFN production. To our knowledge, this is the first report describing the existence and function of the NLRP3 inflammasome in human DCs, and the ability of IAV to prime and activate this pathway in human DCs with important implications for anti-viral immunity and pathogenesis.

APA, Harvard, Vancouver, ISO, and other styles

9

Bencze, Dóra, Tünde Fekete, Walter Pfliegler, Árpád Szöőr, Eszter Csoma, Antónia Szántó, Tünde Tarr, et al. "Interactions between the NLRP3-Dependent IL-1β and the Type I Interferon Pathways in Human Plasmacytoid Dendritic Cells." International Journal of Molecular Sciences 23, no. 20 (October 12, 2022): 12154. http://dx.doi.org/10.3390/ijms232012154.

Full text

Abstract:

Generally, a reciprocal antagonistic interaction exists between the antiviral type I interferon (IFN) and the antibacterial nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain containing 3 (NLRP3)-dependent IL-1β pathways that can significantly shape immune responses. Plasmacytoid dendritic cells (pDCs), as professional type I IFN-producing cells, are the major coordinators of antiviral immunity; however, their NLRP3-dependent IL-1β secretory pathway is poorly studied. Our aim was to determine the functional activity of the IL-1β pathway and its possible interaction with the type I IFN pathway in pDCs. We found that potent nuclear factor-kappa B (NF-κB) inducers promote higher levels of pro-IL-1β during priming compared to those activation signals, which mainly trigger interferon regulatory factor (IRF)-mediated type I IFN production. The generation of cleaved IL-1β requires certain secondary signals in pDCs and IFN-α or type I IFN-inducing viruses inhibit IL-1β production of pDCs, presumably by promoting the expression of various NLRP3 pathway inhibitors. In line with that, we detected significantly lower IL-1β production in pDCs of psoriasis patients with elevated IFN-α levels. Collectively, our results show that the NLRP3-dependent IL-1β secretory pathway is inducible in pDCs; however, it may only prevail under inflammatory conditions, in which the type I IFN pathway is not dominant.

APA, Harvard, Vancouver, ISO, and other styles

10

Wang, Minan, and Sandra Gollnick. "NLRP3 inflammasome independent release of IL-1β by tumor cell lysates stimulated dendritic cells (P2215)." Journal of Immunology 190, no. 1_Supplement (May 1, 2013): 170.64. http://dx.doi.org/10.4049/jimmunol.190.supp.170.64.

Full text

Abstract:

Abstract Photodynamic therapy (PDT) has long been known for capable of killing tumor cells and induces anti-tumor immunity. The mechanism of how PDT can enhance anti-tumor response is not clear. We tested the hypothesis that bone marrow derived dendritic cells (BMDCs) activated by PDT-generated tumor cell lysates (PDTTCL) can induce anti-tumor response in Lewis lung carcinoma (LLC), a poorly immunogenic tumor model. We found that LLC tumor growth was retarded by immunization with BMDCs pulsed by PDTTCL. Furthermore, therapeutic effects are observed in preexisting LLC tumor when PDT is combined with PDTTCL treated BMDCs and R848 (TLR7/8 ligand) therapy. This study aims to understand how PDT enhances tumor immunogenicity and provides insight to improve both in situ PDT and PDT vaccine efficacy in combating secondary disease. We found that stimulation of BMDCs with PDTTCL leads to dramatic increase in pro-inflammatory cytokine production, including IL-1β, which plays a critical role in PDT efficacy. Previous studies have shown that production and activation of IL-1β require both TLR signaling and activation of NLRP3 inflammasome. IL-1β production induced by PDTTCL in BMDCs is MyD88 dependent, but the activation of IL-1β appears to be dependent upon elastase and proteinase 3 rather than NLRP3 inflammasome. Together, our findings reveal a novel mechanism of IL-1β activation in BMDCs that does not require NLRP3 inflammasome in response to danger signals from tumor cell lysates.

APA, Harvard, Vancouver, ISO, and other styles

11

Li, Tianshu, Matthias Zehner, Jieyan He, Tomasz Próchnicki, Gabor Horvath, Eicke Latz, Sven Burgdorf, and Shinji Takeoka. "NLRP3 inflammasome-activating arginine-based liposomes promote antigen presentations in dendritic cells." International Journal of Nanomedicine Volume 14 (May 2019): 3503–16. http://dx.doi.org/10.2147/ijn.s202379.

Full text

APA, Harvard, Vancouver, ISO, and other styles

12

Espinoza, J. Luis, Kosuke Kamio, Vu Quang Lam, and Akiyoshi Takami. "The Impact of NLRP3 Activation on Hematopoietic Stem Cell Transplantation." International Journal of Molecular Sciences 22, no. 21 (October 31, 2021): 11845. http://dx.doi.org/10.3390/ijms222111845.

Full text

Abstract:

NLR family pyrin domain-containing 3 (NLRP3) is an intracellular protein that after recognizing a broad spectrum of stressors, such as microbial motifs and endogenous danger signals, promotes the activation and release of the pro-inflammatory cytokines IL-1β and IL-18, thus playing an essential role in the innate immune response. Several blood cell types, including macrophages, dendritic cells, and hematopoietic stem and progenitor cells (HSPCs), express NLRP3, where it has been implicated in various physiological and pathological processes. For example, NLRP3 participates in the development and expansion of HSPCs, and their release from bone marrow into the peripheral blood has been implicated in certain hematological disorders including various types of leukemia. In addition, accumulating evidence indicates that activation of NLRP3 plays a pivotal role in the development of transplant complications in patients receiving hematopoietic stem cell transplantation (HSCT) including graft versus host disease, severe infections, and transplant-related mortality. The majority of these complications are triggered by the severe tissue damage derived from the conditioning regimens utilized in HSCT which, in turn, activates NLRP3 and, ultimately, promotes the release of proinflammatory cytokines such as IL-1β and IL-18. Here, we summarize the implications of NLRP3 in HSCT with an emphasis on the involvement of this inflammasome component in transplant complications.

APA, Harvard, Vancouver, ISO, and other styles

13

Kannan, Muthukumar, Seema Singh, Divya T. Chemparathy, Abiola A. Oladapo, Dinesh Y. Gawande, Shashank M. Dravid, Shilpa Buch, and Susmita Sil. "HIV-1 Tat induced microglial EVs leads to neuronal synaptodendritic injury: microglia-neuron cross-talk in NeuroHIV." Extracellular Vesicles and Circulating Nucleic Acids 3, no. 2 (2022): 133–49. http://dx.doi.org/10.20517/evcna.2022.14.

Full text

Abstract:

Aim: Activation of microglial NLRP3 inflammasome is an essential contributor to neuroinflammation underlying HIV-associated neurological disorders (HAND). Under pathological conditions, microglia-derived-EVs (MDEVs) can affect neuronal functions by delivering neurotoxic mediators to recipient cells. However, the role of microglial NLRP3 in mediating neuronal synaptodendritic injury has remained unexplored to date. In the present study, we sought to assess the regulatory role of HIV-1 Tat induced microglial NLRP3 in neuronal synaptodendritic injury. We hypothesized that HIV-1 Tat mediated microglia EVs carrying significant levels of NLRP3 contribute to the synaptodendritic injury, thereby affecting the maturation of neurons. Methods: To understand the cross-talk between microglia and neuron, we isolated EVs from BV2 and human primary microglia (HPM) cells with or without NLRP3 depletion using siNLRP3 RNA. EVs were isolated by differential centrifugation, characterized by ZetaView nanoparticle tracking analysis, electron microscopy, and western blot analysis for exosome markers. Purified EVs were exposed to primary rat neurons isolated from E18 rats. Along with green fluorescent protein (GFP) plasmid transfection, immunocytochemistry was performed to visualize neuronal synaptodendritic injury. Western blotting was employed to measure siRNA transfection efficiency and the extent of neuronal synaptodegeneration. Images were captured in confocal microscopy, and subsequently, Sholl analysis was performed for analyzing dendritic spines using neuronal reconstruction software Neurolucida 360. Electrophysiology was performed on hippocampal neurons for functional assessment. Results: Our findings demonstrated that HIV-1 Tat induced expression of microglial NLRP3 and IL1β, and further that these were packaged in microglial exosomes (MDEV) and were also taken up by the neurons. Exposure of rat primary neurons to microglial Tat-MDEVs resulted in downregulation of synaptic proteins- PSD95, synaptophysin, excitatory vGLUT1, as well as upregulation of inhibitory proteins- Gephyrin, GAD65, thereby implicating impaired neuronal transmissibility. Our findings also showed that Tat-MDEVs not only caused loss of dendritic spines but also affected numbers of spine sub-types- mushroom and stubby. Synaptodendritic injury further affected functional impairment as evidenced by the decrease in miniature excitatory postsynaptic currents (mEPSCs). To assess the regulatory role of NLRP3 in this process, neurons were also exposed to Tat-MDEVs from NLRP3 silenced microglia. Tat-MDEVs from NLRP3 silenced microglia exerted a protective role on neuronal synaptic proteins, spine density as well as mEPSCs. Conclusion: In summary, our study underscores the role of microglial NLRP3 as an important contributor to Tat-MDEV mediated synaptodendritic injury. While the role of NLRP3 in inflammation is well-described, its role in EV-mediated neuronal damage is an interesting finding, implicating it as a target for therapeutics in HAND.

APA, Harvard, Vancouver, ISO, and other styles

14

Abas, Razif, Rusliza Basir, Suryati Mohd Thani, Safuraa Salihan, Azmah Saat, Nurul Hayati Mohamad Zainal, Siti Fadziyah Mohamad Asri, Nur Izah Ab Razak, Nurul Huda Mohd Nor, and Nur Aqilah Kamaruddin. "The Evolving Role of Nucleotide-binding Oligomerisation Domain-like Receptor Pyrin Domain 3 Inflammasome Activation in Vascular Endothelial Cells: A Review." Malaysian Journal of Medical Sciences 29, no. 2 (April 21, 2022): 8–17. http://dx.doi.org/10.21315/mjms2022.29.2.2.

Full text

Abstract:

In the vascular wall, defence against pathogenic damage requires a group of monocytes, the endothelium, dendritic cells, macrophages and a subsequent involvement of pattern recognition receptors anticipating damage-associated molecular patterns (DAMPs) to initiate an innate immune response. The endothelium plays a crucial role in regulating the duration, location and extent of the inflammatory cascade to ensure a definitive immune defence. Molecular changes in the expression of chemokines and cell adhesion molecules ensure protective responses against infection and injury. The multiprotein oligomer complex nucleotide-binding oligomerisation domain (NOD)-like receptor pyrin domain 3 (NLRP3) inflammasome plays a key role in the activation of inflammatory processes in response to DAMPs and pattern-associated molecular patterns. As a result of NLRP3 inflammasome activation, caspase-1 is activated and interleukin-1β (IL-1β) is produced. Caspase-1 is the main mediator of inflammatory feedback to tissue injury, and it is engaged both in the initiation of the inflammatory response and in the induction of cell death. NLRP3 inflammasome promotes further inflammatory responses and pyroptosis in the vascular endothelium; thus, its optimum regulation is crucial in cardiovascular homeostasis. This review outlines our current perception of the role of NLRP3 in vascular endothelial cells.

APA, Harvard, Vancouver, ISO, and other styles

15

Paget, Christophe, Emilie Doz-Deblauwe, Nathalie Winter, and Benoit Briard. "Specific NLRP3 Inflammasome Assembling and Regulation in Neutrophils: Relevance in Inflammatory and Infectious Diseases." Cells 11, no. 7 (April 1, 2022): 1188. http://dx.doi.org/10.3390/cells11071188.

Full text

Abstract:

The NLRP3 inflammasome is a cytosolic multimeric protein platform that leads to the activation of the protease zymogen, caspase-1 (CASP1). Inflammasome activation mediates the proteolytic activation of pro-inflammatory cytokines (IL-1β and IL-18) and program cell death called pyroptosis. The pyroptosis is mediated by the protein executioner Gasdermin D (GSDMD), which forms pores at the plasma membrane to facilitate IL-1β/IL-18 secretion and causes pyroptosis. The NLRP3 inflammasome is activated in response to a large number of pathogenic and sterile insults. However, an uncontrolled inflammasome activation may drive inflammation-associated diseases. Initially, inflammasome-competent cells were believed to be limited to macrophages, dendritic cells (DC), and monocytes. However, emerging evidence indicates that neutrophils can assemble inflammasomes in response to various stimuli with functional relevance. Interestingly, the regulation of inflammasome in neutrophils appears to be unconventional. This review provides a broad overview of the role and regulation of inflammasomes—and more specifically NLRP3—in neutrophils.

APA, Harvard, Vancouver, ISO, and other styles

16

Jankovic, Dragana, Jayanthi Ganesan, Michael Bscheider, Natalie Stickel, Felix C. Weber, Greta Guarda, Marie Follo, et al. "The Nlrp3 inflammasome regulates acute graft-versus-host disease." Journal of Experimental Medicine 210, no. 10 (August 26, 2013): 1899–910. http://dx.doi.org/10.1084/jem.20130084.

Full text

Abstract:

The success of allogeneic hematopoietic cell transplantation is limited by acute graft-versus-host disease (GvHD), a severe complication accompanied by high mortality rates. Yet, the molecular mechanisms initiating this disease remain poorly defined. In this study, we show that, after conditioning therapy, intestinal commensal bacteria and the damage-associated molecular pattern uric acid contribute to Nlrp3 inflammasome–mediated IL-1β production and that gastrointestinal decontamination and uric acid depletion reduced GvHD severity. Early blockade of IL-1β or genetic deficiency of the IL-1 receptor in dendritic cells (DCs) and T cells improved survival. The Nlrp3 inflammasome components Nlrp3 and Asc, which are required for pro–IL-1β cleavage, were critical for the full manifestation of GvHD. In transplanted mice, IL-1β originated from multiple intestinal cell compartments and exerted its effects on DCs and T cells, the latter being preferentially skewed toward Th17. Compatible with these mouse data, increased levels of active caspase-1 and IL-1β were found in circulating leukocytes and intestinal GvHD lesions of patients. Thus, the identification of a crucial role for the Nlrp3 inflammasome sheds new light on the pathogenesis of GvHD and opens a potential new avenue for the targeted therapy of this severe complication.

APA, Harvard, Vancouver, ISO, and other styles

17

Fernandez, Melissa Victoria, Elizabeth Miller, Florian Krammer, Ramya Gopal, Benjamin D. Greenbaum, and Nina Bhardwaj. "Ion efflux and influenza infection trigger NLRP3 inflammasome signaling in human dendritic cells." Journal of Leukocyte Biology 99, no. 5 (November 16, 2015): 723–34. http://dx.doi.org/10.1189/jlb.3a0614-313rrr.

Full text

APA, Harvard, Vancouver, ISO, and other styles

18

Hamarsheh, Shaima'A, Miriam Erlacher, Lena Osswald, Oliver Gorka, Justus Duyster, Olaf Groß, Claudia Lengerke, Melanie Börries, Tilman Brummer, and Robert Zeiser. "Oncogenic KRASG12D in the Hematopoietic System Causes NLRP3 Inflammasome Activation Leading to Myeloproliferative Syndrome." Blood 132, Supplement 1 (November 29, 2018): 2618. http://dx.doi.org/10.1182/blood-2018-99-114161.

Full text

Abstract:

Abstract Oncogenic Ras mutations occur frequently in myelodysplastic (MDS) and myeloproliferative syndromes (MPN). It was unclear if besides the direct transforming effect via constant RAS/MEK/ERK signaling, an inflammation related effect of KRAS contributes to the development of the disease. To address this question we performed a microarray based analysis of bone marrow derived from Rosa26CreERT2; LSL-KrasG12D mice after induction of KrasG12D with tamoxifen. We found that the NLRP3 inflammasome and related genes were upregulated. In agreement with increased NLRP3 sensitivity, KrasG12D bone marrow derived dendritic cells (BMDCs) showed increased inflammasome activation upon stimulation with LPS and ATP as quantified by intracellular levels of IL-1β and caspase-1 p20 subunit. To validate the functional role of the NLRP3 inflammasome for the MDS phenotype in vivo we generated Rosa26CreERT2; LSL-KrasG12D; NLRP3-/- mice. We transferred BM (CD45.2) from WT mice, Rosa26CreERT2; LSL-KrasG12D or Rosa26CreERT2; LSL-KrasG12D; NLRP3-/- mice into C57BL/6 WT recipients (CD45.1) after myeloablative conditioning and induced KrasG12D by tamoxifen treatment. Rosa26CreERT2; LSL-KrasG12D BM recipient mice developed MPN stigmata including anemia, leukopenia and thrombocytopenia. The mice also presented weight loss, splenomegaly, and an increase in myeloid cells in peripheral blood, spleen and BM, as well as increased CD11b+ckit+ immature myeloid progenitors. In contrast, Rosa26CreERT2; LSL-KrasG12D; NLRP3-/- recipient mice developed no disease phenotype. BMDCs isolated from Rosa26CreERT2; LSL-KrasG12D recipient mice exhibited strong NLRP3 inflammasome activation and high IL-1β levels which was not found in BMDCs of Rosa26CreERT2; LSL-KrasG12D; NLRP3-/- mice. CD11b+ cells of a Juvenile myelomonocytic leukemia (JMML) patient with an activating KRAS mutation showed increased inflammasome activation as compared to a non-mutant patient, which is in agreement with our observations in mouse models. Our findings support the concept that oncogenic KrasG12D does not only act via its oncogenic driver function, but also enhances activation of the NLRP3/IL-1β axis. This could lead to novel therapeutic approaches combining inhibition of oncogenic signaling and immune modulation via IL-1β blockade. Disclosures No relevant conflicts of interest to declare.

APA, Harvard, Vancouver, ISO, and other styles

19

Han, Chuanhui, Victoria Godfrey, Zhida Liu, Yanfei Han, Longchao Liu, Hua Peng, Ralph R. Weichselbaum, Hasan Zaki, and Yang-Xin Fu. "The AIM2 and NLRP3 inflammasomes trigger IL-1–mediated antitumor effects during radiation." Science Immunology 6, no. 59 (May 7, 2021): eabc6998. http://dx.doi.org/10.1126/sciimmunol.abc6998.

Full text

Abstract:

The inflammasome promotes inflammation-associated diseases, including cancer, and contributes to the radiation-induced tissue damage. However, the role of inflammasome in radiation-induced antitumor effects is unclear. We observed that tumors transplanted in Casp1−/− mice were resistant to radiation treatment compared with tumors in wild-type (WT) mice. To map out which molecule in the inflammasome pathway contributed to this resistant, we investigated the antitumor effect of radiation in several inflammasome-deficient mice. Tumors grown in either Aim2−/− or Nlrp3−/− mice remained sensitive to radiation, like WT mice, whereas Aim2−/−Nlrp3−/− mice showed radioresistance. Mechanistically, extracellular vesicles (EVs) and EV-free supernatant derived from irradiated tumors activated both Aim2 and Nlrp3 inflammasomes in macrophages, leading to the production of interleukin-1β (IL-1β). IL-1β treatment helped overcome the radioresistance of tumors growing in Casp1−/− and Aim2−/−Nlrp3−/− mice. IL-1 signaling in dendritic cells (DCs) promoted radiation-induced antitumor immunity by enhancing the cross-priming activity of DCs. Overall, we demonstrated that radiation-induced activation of the AIM2 and NLRP3 inflammasomes coordinate to induce some of the antitumor effects of radiation by triggering IL-1 signaling in DCs, leading to their activation and cross-priming.

APA, Harvard, Vancouver, ISO, and other styles

20

Yashiro, Takuya, Machiko Yamamoto, Sanae Araumi, and Chiharu Nishiyama. "PU.1 and IRF8 modulate the activation of NLRP3 inflammasome via regulating the monocyte-specific expression of the NLRP3 and its component genes." Journal of Immunology 204, no. 1_Supplement (May 1, 2020): 69.29. http://dx.doi.org/10.4049/jimmunol.204.supp.69.29.

Full text

Abstract:

Abstract NLRP3 inflammasome plays crucial roles in the host defense against pathogens by activating Caspase-1, which catalyzes the processing of immature IL-1β and IL-18 into a biologically active form. NLRP3 expression is restricted in monocytic lineages such as monocytes, macrophages, and dendritic cells, thus its expression must be strictly regulated. However, the regulatory mechanism of lineage-specific transcription of the NLRP3 gene remains largely unknown. In this study, we investigated the molecular mechanisms of cell-type specific NLRP3 expression. RT-PCR revealed that the NLRP3 gene was dominantly driven from the distal promoter in a human monocytic cell line, THP-1. By reporter assay, we identified several cis-acting elements including an Ets/IRF composite element (EICE), which is frequently associated with monocytic lineage-specific gene regulation, in the distal promoter of the human NLRP3 gene. EMSA and ChIP assay demonstrated that transcription factors, PU.1 and IRF8, both of which are known to play essential roles in the development of monocytic lineage, cooperatively bind to the EICE. The expression of NLRP3 was significantly decreased by the siRNA-mediated knockdown of PU.1 and/or IRF8. In addition, the knockdown of PU.1 and/or IRF8 down-regulated the expression of ASC and Caspase-1, which form inflammasome complex with NLRP3. Furthermore, we found that the silencing of PU.1 and IRF8 dramatically abrogated the processing of pro-IL-1β. These results indicate that PU.1 and IRF8 are involved in the monocytic lineage-specific NLRP3 expression by binding to the EICE site within the distal promoter.

APA, Harvard, Vancouver, ISO, and other styles

21

Rhoads, Jillian, Ashley Wilhelm, Jared Moore, and Amy Major. "Oxidized low density lipoprotein immune complexes act as a priming signal for the NLRP3 inflammasome (HUM1P.253)." Journal of Immunology 194, no. 1_Supplement (May 1, 2015): 52.2. http://dx.doi.org/10.4049/jimmunol.194.supp.52.2.

Full text

Abstract:

Abstract Antibodies to oxidized LDL (oxLDL) and resulting immune complexes (ICs) are a prominent feature of atherosclerosis and autoimmune diseases associated with increased atherosclerosis. Although levels of oxLDL-ICs correlate with disease severity, it is unclear whether these ICs play an active role in disease pathogenesis. We hypothesize that oxLDL-ICs exacerbate atherosclerosis by signaling through multiple receptors on dendritic cells (DCs) resulting in an inflammatory adaptive immune response. To test this hypothesis, bone marrow derived dendritic cells (BMDC) were incubated with oxLDL or oxLDL-IC and cytokine levels in culture supernatants were measured by ELISA. Results indicated a 10-fold increase in IL-1β production from BMDC treated with oxLDL-IC compared to oxLDL, suggesting a role for the inflammasome in oxLDL-IC activation of DC. Pre-treatment of BMDC with a caspase 1 inhibitor and use of NLRP3-/- BMDC abolished IL-1β secretion in response to oxLDL-IC, further implicating the inflammasome. Additional investigation using Fab fragments and a TLR4 inhibitor uncovered a role for both FcγR and TLR4 in oxLDL-IC mediated IL-1β production. Finally, BMDC pre-treated with oxLDL-IC, but not oxLDL, and incubated with CD4+ OT-II T cells in the presence of OVA peptide skewed T cells towards a Th17 phenotype. Taken together, these data suggest a novel and pathologic role of oxLDL-ICs in activating the NLRP3 inflammasome and promoting an inflammatory T cell phenotype.

APA, Harvard, Vancouver, ISO, and other styles

22

Katsnelson, Michael A., Kristen M. Lozada-Soto, Hana M. Russo, Barbara A. Miller, and George R. Dubyak. "NLRP3 inflammasome signaling is activated by low-level lysosome disruption but inhibited by extensive lysosome disruption: roles for K+ efflux and Ca2+ influx." American Journal of Physiology-Cell Physiology 311, no. 1 (July 1, 2016): C83—C100. http://dx.doi.org/10.1152/ajpcell.00298.2015.

Full text

Abstract:

Nucleotide-binding domain, leucine-rich-repeat-containing family, pyrin domain-containing 3 (NLRP3) is a cytosolic protein that nucleates assembly of inflammasome signaling platforms, which facilitate caspase-1-mediated IL-1β release and other inflammatory responses in myeloid leukocytes. NLRP3 inflammasomes are assembled in response to multiple pathogen- or environmental stress-induced changes in basic cell physiology, including the destabilization of lysosome integrity and activation of K+-permeable channels/transporters in the plasma membrane (PM). However, the quantitative relationships between lysosome membrane permeabilization (LMP), induction of increased PM K+ permeability, and activation of NLRP3 signaling are incompletely characterized. We used Leu-Leu- O-methyl ester (LLME), a soluble lysosomotropic agent, to quantitatively track the kinetics and extent of LMP in relation to NLRP3 inflammasome signaling responses (ASC oligomerization, caspase-1 activation, IL-1β release) and PM cation fluxes in murine bone marrow-derived dendritic cells (BMDCs). Treatment of BMDCs with submillimolar (≤1 mM) LLME induced slower and partial increases in LMP that correlated with robust NLRP3 inflammasome activation and K+ efflux. In contrast, supramillimolar (≥2 mM) LLME elicited extremely rapid and complete collapse of lysosome integrity that was correlated with suppression of inflammasome signaling. Supramillimolar LLME also induced dominant negative effects on inflammasome activation by the canonical NLRP3 agonist nigericin; this inhibition correlated with an increase in NLRP3 ubiquitination. LMP elicited rapid BMDC death by both inflammasome-dependent pyroptosis and inflammasome-independent necrosis. LMP also triggered Ca2+ influx, which attenuated LLME-stimulated NLRP3 inflammasome signaling but potentiated LLME-induced necrosis. Taken together, these studies reveal a previously unappreciated signaling network that defines the coupling between LMP, changes in PM cation fluxes, cell death, and NLRP3 inflammasome activation.

APA, Harvard, Vancouver, ISO, and other styles

23

Sebastião, Ana Isabel, Isabel Ferreira, Gonçalo Brites, Ana Silva, Bruno Miguel Neves, and Maria Teresa Cruz. "NLRP3 Inflammasome and Allergic Contact Dermatitis: A Connection to Demystify." Pharmaceutics 12, no. 9 (September 11, 2020): 867. http://dx.doi.org/10.3390/pharmaceutics12090867.

Full text

Abstract:

Allergic contact dermatitis is a common occupational disease that manifests as a cell-mediated hypersensitivity reaction following skin exposure to small reactive chemicals termed haptens. Haptens penetrate the stratum corneum and covalently modify proteins in the epidermis, inducing intracellular stress, which further leads to the release of damage-associated molecular patterns (DAMPs), such as uric acid, reactive oxygen species, hyaluronic acid fragments and extracellular adenosine triphosphate (ATP). These DAMPs are recognized by pattern recognition receptors (PRRs) in innate immune cells, namely dendritic cells (DCs), leading to their maturation and migration to the draining lymph nodes where they activate naïve T lymphocytes. Among all PRRs, several studies emphasize the role of NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome on the allergic contact dermatitis (ACD) sensitization phase. However, skin allergens—danger signals—NLRP3 inflammasome axis is yet to be completely elucidated. Therefore, in this review, we sought to discuss the molecular mechanisms underlying DAMPs release and NLRP3 inflammasome activation triggered by skin allergens. The elucidation of these key events might help to identify novel therapeutic strategies for ACD, as well as the development of nonanimal alternative methods for the identification and potency categorization of skin sensitizers.

APA, Harvard, Vancouver, ISO, and other styles

24

Raychaudhuri, Kumarkrishna, Anthony St Leger, Fatimah Almaghrabi, Ivan J. Fuss, Warren Strober, and Rachel R. Caspi. "An aberrant immune response to an ocular commensal results in disease in a mouse model of Muckle-Wells Syndrome." Journal of Immunology 198, no. 1_Supplement (May 1, 2017): 55.43. http://dx.doi.org/10.4049/jimmunol.198.supp.55.43.

Full text

Abstract:

Abstract Appropriate regulation of host immunity by commensal bacteria at mucosal tissues, including the ocular surface, can prevent infection and limit disease. Our recent data (St. Leger et al, this conference) suggest that Corynebacterium mastitidis (=C. mast), an ocular commensal, elicits production of protective IL-17 from conjunctival gdT cells. What is not known is whether this relationship, when dysregulated, can lead to pathology and disease. In this study, we used a mouse model of Muckle-Wells Syndrome (MWS), which is a human autoinflammatory disease that results in spontaneous inflammation of the conjunctiva, skin and joints. This is caused by a mutation in the NLRP3 gene (cias1) that leads to an overactive NLRP3 inflammasome and results in production of multiple proinflammatory cytokines, including, most prominently, IL-1b. Here, we show that ocular colonization with a commensal bacterium, C. mast, induces ocular inflammation in MWS mice, but not in WT controls. Dendritic cells from MWS mice produced increased amounts of IL-1b upon stimulation with C. mast lysates. In keeping with this, DCs harvested from MWS mice more efficiently activated gdT cells (in particular, Vγ4+ cells) in co-culture experiments, compared to DCs from WT mice. Our results suggest that the commensal C. mast can act as a pathobiont and trigger ocular inflammation in mice with an overactive NLRP3 inflammasome. Thus, an aberrant immune response to commensal microbes in humans with this mutation may be the cause of recurrent conjunctivitis in patients with MWS or similar autoinflammatory diseases.

APA, Harvard, Vancouver, ISO, and other styles

25

Wu-Hsieh, Betty, Tzu-Hsuan Chang, and Juin-Hua Huang. "Dectin-2 as a Primary Receptor for NLRP3-inflammasome Activation in Dendritic Cell Responses to Histoplasma capsulatum." Journal of Immunology 198, no. 1_Supplement (May 1, 2017): 77.23. http://dx.doi.org/10.4049/jimmunol.198.supp.77.23.

Full text

Abstract:

Abstract Inflammasome is an intracellular protein complex that serves as cytosolic pattern recognition receptor (PRR) to engage with pathogens and to process cytokines of the interleukin-1 (IL-1) family into bioactive molecules. It has been established that interleukin-1β (IL-1β) is important to host defense against Histoplasma capsulatum infection. However, the detailed mechanism of how H. capsulatum induces inflammasome activation leading to IL-1β production has not been studied. Here, we showed in dendritic cells (DCs) that H. capsulatum triggers caspase-1 activation and IL-1β production through NLRP3 inflammasome. By reciprocal blocking of Dectin-1 or Dectin-2 in receptor-deficient DCs, we discovered that while Dectin-2 operates as a primary receptor, Dectin-1 serves as a secondary one for NLRP3 inflammasome. Both receptors trigger Syk-JNK signal pathway to activate both signal 1 (the transcription of Il1b) and signal 2 (activation of caspase-1). While both K+ efflux and cathepsin B (but not ROS) function as signal 2, viable H. capsulatum triggers profound lysosomal rupture leading to cathepsin B release. Our study demonstrates the role of Dectin-2 and Dectin-1 in host defense against H. capsulatum infection through induction of NLRP3 inflammasome activation and IL-1b production in DCs.

APA, Harvard, Vancouver, ISO, and other styles

26

Jang, Hye-Mi, Ji-Yeon Park, Yeon-Ji Lee, Min-Jung Kang, Sung-Gang Jo, Yu-Jin Jeong, Nam-Pyo Cho, Sung-Dae Cho, Dong-Jae Kim, and Jong-Hwan Park. "TLR2 and the NLRP3 inflammasome mediate IL-1β production in Prevotella nigrescens-infected dendritic cells." International Journal of Medical Sciences 18, no. 2 (2021): 432–40. http://dx.doi.org/10.7150/ijms.47197.

Full text

APA, Harvard, Vancouver, ISO, and other styles

27

Zhang, Maomao, Yang Zheng, Yong Sun, Shuang Li, Liangqi Chen, Xiangyuan Jin, Xinyu Hou, et al. "Knockdown of NEAT1 induces tolerogenic phenotype in dendritic cells by inhibiting activation of NLRP3 inflammasome." Theranostics 9, no. 12 (2019): 3425–42. http://dx.doi.org/10.7150/thno.33178.

Full text

APA, Harvard, Vancouver, ISO, and other styles

28

Conforti-Andreoni, Cristina, Ottavio Beretta, Ginevra Licandro, Hong Liang Qian, Matteo Urbano, Federico Vitulli, Paola Ricciardi-Castagnoli, and Alessandra Mortellaro. "Synergism of NOD2 and NLRP3 activators promotes a unique transcriptional profile in murine dendritic cells." Journal of Leukocyte Biology 88, no. 6 (September 30, 2010): 1207–16. http://dx.doi.org/10.1189/jlb.1009652.

Full text

APA, Harvard, Vancouver, ISO, and other styles

29

Licandro, Ginevra, Hwei Ling Khor, Ottavio Beretta, Junyun Lai, Heidi Derks, Federica Laudisi, Cristina Conforti-Andreoni, et al. "The NLRP3 inflammasome affects DNA damage responses after oxidative and genotoxic stress in dendritic cells." European Journal of Immunology 43, no. 8 (May 24, 2013): 2126–37. http://dx.doi.org/10.1002/eji.201242918.

Full text

APA, Harvard, Vancouver, ISO, and other styles

30

GIULIANI, K., M. Rist, X. Wang, B. Law, R. Wilkinson, J. Ungerer, H. Healy, and A. Kassianos. "SUN-149 HUMAN HYPOXIC PROXIMAL TUBULE EPITHELIAL CELLS (PTEC) TRIGGER NLRP3 INFLAMMASOME ACTIVATION IN CD1c+ DENDRITIC CELLS (DC)." Kidney International Reports 4, no. 7 (July 2019): S220. http://dx.doi.org/10.1016/j.ekir.2019.05.550.

Full text

APA, Harvard, Vancouver, ISO, and other styles

31

Adamiak, Mateusz, Anna Lenkiewicz, Kamila Bujko, Arjun Thapa, Magdalena Kucia, Ahmed Abdel-Latif, Janina Ratajczak, and Mariusz Z. Ratajczak. "Novel Evidence That the Nlrp3 Inflammasome Plays a Role in Bone Marrow As a "Cogwheel" Connecting Purinergic Signaling with Activation of the Complement Cascade to Induce "Sterile Inflammation", Which Is Required for Optimal Mobilization of Hematopoietic Stem/Progenitor Cells." Blood 134, Supplement_1 (November 13, 2019): 4468. http://dx.doi.org/10.1182/blood-2019-125838.

Full text

Abstract:

Background . In order to develop more efficient mobilization strategies, we have to better understand the mobilization process at the molecular and cellular levels. We envision pharmacological mobilization of HSPCs as the result of "sterile inflammation" in the bone marrow (BM) microenvironment induced by pro-mobilizing agents (e.g., G-CSF or AMD3100). This leads to activation of the complement cascade (ComC), which is required for egress of HSPCs from BM into peripheral blood (PB) (Leukemia 2018; 32:1116-1123). In support of this hypothesis, we reported recently that BM-residing innate immunity cells (e.g., monocytes, granulocytes and dendritic cells) release adenosine triphosphate (ATP) into the extracellular space during the initiation phase of mobilization. ATP released from the cells is an important signaling molecule that activates purinergic signaling receptors on the surface of hematopoietic cells (Leukemia 2018, 32:1920-1931) and is released mainly by pannexin 1 channels. Inhibition of this channel significantly decreases mobilization efficacy (Leukemia 2018, 32:1920-1931). In addition, ATP in the extracellular BM space is processed by the CD39 and CD73 ectonucleotidases to adenosine (Ado), which inhibits mobilization. To shed more light on the molecular mechanism governing mobilization of HSPCs, we focused on the role of the Nlrp3 inflammasome, which is highly expressed in hematopoietic cells. Moreover, while ATP binds to the P2X7 and P2X4 purinergic receptors and strongly activates Nlrp3, Ado inhibits migration of HSPCs in a heme oxygenase 1 (HO-1)-dependent manner.Hypothesis. We hypothesized that the Nlrp3 inflammasome is a link or "cogwheel" between purinergic signaling and the ComC that orchestrates optimal mobilization of HSPCs. Materials and Methods. To test this hypothesis we first mobilized wild type mice by G-CSF and AMD3100 administration in the presence of the small-molecule Nlrp3 inhibitor MCC950 or the Nlrp3 inflammasome activator nigericin, and the results were subsequently compared with results for Nlrp3-KO mice. Following mobilization, we measured i) the total number of white blood cells (WBCs) and ii) the number of circulating clonogenic colony-forming unit granulocyte/macrophage (CFU-GM) progenitors and Sca-1+c-kit+lineage- (SKL) cells circulating in PB. The secretion of ATP from BM cells was inhibited by employing the pannexin-1-blocking drug probenecid or a synthetic pannexin-1-blocking peptide (Panx-1). Nlrp3 inflammasome mRNA expression was measured in BM innate immunity cells, CD11b/Gr-1+ cells, and CD11b/Gr-1+ cells isolated under steady-state conditions from mobilized mice stimulated with ATP or Ado. Elements of the activated inflammasome, such as caspase-1, IL-1b, and IL-18, were measured at the mRNA (RT-PCR) and protein (ELISA) levels. In parallel, we evaluated i) the expression of HO-1 in HSPCs by employing RQ-PCR and western blot analysis and ii) activation of the ComC by C5a ELISA. Results. While mobilization of HSPCs was significantly decreased in P2X7-KO mice and mice with Nlrp3 inflammasome deficiency, it was significantly increased in the presence of the Nlrp3 inflammasome activator nigericin. Proper activation of the inflammasome required ATP release in a pannexin-1-dependent manner and stimulation of hematopoietic cells in a P2X7 purinergic receptor-dependent manner. Moreover, Ado inhibited the mobilization process by upregulating HO-1 in HSPCs, which, as we observed, inhibits the Nlrp3 inflammasome in HSPCs. Finally, while activation of the Nlrp3 inflammasome was positively correlated with activation of the ComC, inhibition of the Nlrp3 inflammasome had the opposite effect. Conclusions. We demonstrate for the first time that purinergic signaling involving ATP and its metabolite adenosine regulate the mobilization of HSPCs in an Nlrp3 inflammasome-dependent manner. While ATP triggers and promotes this process via activation of the Nlrp3 inflammasome, adenosine has an inhibitory effect by upregulating HO-1 (Figure 1). Based on these findings, stimulation of the Nlrp3 inflammasome by ATP, inhibiting the Ado level by small-molecule inhibitors of the CD39 or CD73 enzymes involved in generation of extracellular Ado, or direct inhibition of HO-1 in HSPCs by employing small-molecule inhibitors may provide the basis for more efficient mobilization strategies. Figure 1 Disclosures No relevant conflicts of interest to declare.

APA, Harvard, Vancouver, ISO, and other styles

32

Moreira, Jôsimar Dornelas, Ramakrishna Vankayalapati, and Buka Samten. "Histone deacetylase-1 controls IL-1β production through the regulation of NLRP3 expression and activation in tuberculosis infection." Journal of Immunology 206, no. 1_Supplement (May 1, 2021): 99.11. http://dx.doi.org/10.4049/jimmunol.206.supp.99.11.

Full text

Abstract:

Abstract Although IL-1b is required for the protection against Mycobacterium tuberculosis (Mtb) infection, its uncontrolled production is associated with chronic inflammation and lung damage in Tuberculosis. Epigenetic effector molecules histone deacetylases (HDACs) play critical roles in tumorigenesis and immune regulation, however their roles in IL-1β production remain unexplored. Initial screening of 11 variants of HDAC with their chemical inhibitors identified that inhibition of HDAC-1 promotes secretion of IL-1β and increases the lysine acetylation of histone H3 by primary macrophages and dendritic cells (DCs) in response to LPS/CD40L, IFN-γ stimulation or Mtb infection without affecting pro-IL-1β and IL-6. Inhibition of NLRP3 or Caspase-1 reversed this effect of HDAC-1 inhibition without affecting cell viability, implying the involvement of NLRP3 inflammasome activation. Consistently, HDAC-1 inhibition further elevated the expression of both mRNA and protein of NLRP3 in macrophages and DCs under stimulation and increased levels of cleaved Caspase-1 and mature IL-1β in the culture supernatants. Mtb infection and stimulation with LPS/CD40L of these cells induced increased expression and phosphorylation of HDAC-1 and increased HDAC-1 activity in cell lysates which was suppressed by HDAC-1 inhibitor. Treatment of low dose aerosol Mtb-infected mice with HDAC-1 inhibitor increased IL-1β in mice lungs without affecting IL-6 production. These suggest that HDAC-1 controls IL-1β maturation via regulation of NLRP3 expression and activation, thus suggesting a novel mechanism for the regulation of IL-1β, a major inflammatory cytokine in tuberculosis infection and other inflammatory diseases.

APA, Harvard, Vancouver, ISO, and other styles

33

Shi, Gao-Na, Min Hu, Chengjuan Chen, Junmin Fu, Shuai Shao, Yu Zhou, Lei Wu, and Tiantai Zhang. "Methotrexate enhances antigen presentation and maturation of tumour antigen-loaded dendritic cells through NLRP3 inflammasome activation: a strategy for dendritic cell-based cancer vaccine." Therapeutic Advances in Medical Oncology 13 (January 2021): 175883592098705. http://dx.doi.org/10.1177/1758835920987056.

Full text

Abstract:

Background: Dendritic cells (DCs) are antigen-presenting cells that play a pivotal role in adaptive cell-mediated immunity by priming and activating T cells against specific tumour and pathogenic antigens. Methotrexate (MTX), a folate derivative, functions as an immunoregulatory agent. However, the possible effect of MTX on tumour antigen-loaded DCs has not yet been investigated. Methods: We analysed the effect of MTX on the maturation and function of DCs along with tumour cell lysates (TCLs). Using bone marrow-derived DCs, we investigated the effect of MTX combined TCL-loaded DCs on T cells priming and proliferation. We also tested the anti-tumour immune effect on DCs when treated with MTX and/or TCL in vivo. Results: MTX combined with TCL not only enhanced DC maturation and stimulated cytokine release but also promoted CD8+ T cell activation and proliferation. The latter was associated with increased tumour antigen uptake and cross-presentation to T cells. Mechanistically, DC maturation and antigen presentation were partly modulated by NLRP3 inflammasome activation. Furthermore, immunisation of mice with MTX and TCL-pulsed DCs before a tumour challenge significantly delayed tumour onset and retarded its growth. This protective effect was due to priming of IFN-γ releasing CD8+ T cells and enhanced killing of tumour cells by cytotoxic T lymphocytes isolated from these immunised mice. Conclusion: MTX can function as a potent adjuvant in DC vaccines by increasing antigen presentation and T cell priming. Our findings provide a new strategy for the application of DC-based anti-tumour immunotherapy.

APA, Harvard, Vancouver, ISO, and other styles

34

Clark, Sarah E., Rebecca L. Schmidt, Daniel S. McDermott, and Laurel L. Lenz. "IL-18 from Batf3-dependent cells licenses natural killer cell IL-10 production during Listeria monocytogenes infection." Journal of Immunology 200, no. 1_Supplement (May 1, 2018): 114.1. http://dx.doi.org/10.4049/jimmunol.200.supp.114.1.

Full text

Abstract:

Abstract Natural killer (NK) cells are innate lymphoid cells that regulate the immune response to infection through secretion of both pro- and anti-inflammatory cytokines. The pathogen Listeria monocytogenes (Lm) capitalizes on NK cell production of the anti-inflammatory cytokine interleukin (IL)-10 during establishment of severe infection. Lm-stimulated NK cell IL-10 limits immune cell recruitment and activation, allowing for bacterial expansion. Here, we report that IL-18 from dendritic cells (DCs) promotes this IL-10 production. IL-18 acts directly on NK cells to license IL-10 secretion that is independent of IL-12 and STAT4, which co-stimulate IFNγ secretion during Lm infection and can induce NK cell IL-10 in other contexts. DC release of IL-18 is driven by the Lm p60 virulence protein and requires DC expression of nlrp3 and batf3. Mice lacking nlrp3, il18, il18R, or batf3 fail to accumulate serum IL-10 and are highly resistant to systemic Lm infection. Our data thus show that during systemic infection Lm selectively targets Baft3-dependent cells to drive IL-18 release that licenses NK cell IL-10 production. Exploiting this previously-unappreciated pathway to promote IL-10 production enables Lm to dampen inflammatory and anti-microbial host responses.

APA, Harvard, Vancouver, ISO, and other styles

35

Antonopoulos, Christina, and George Dubyak. "Chemotherapeutic drugs trigger rapid apoptotic induction and caspase-1/ inflammasome signaling in murine macrophages (46.33)." Journal of Immunology 188, no. 1_Supplement (May 1, 2012): 46.33. http://dx.doi.org/10.4049/jimmunol.188.supp.46.33.

Full text

Abstract:

Abstract The success of certain cancer chemotherapy drugs relies critically on the host immune system. In some cancer models, induction of NLRP3/caspase-1/IL-1β signaling cascades in dendritic cells is required for effective anti-tumor immunity. Recent studies by Sauter et al. (Cancer Biol Ther 2010) reported (and we have confirmed) that the chemotherapeutic anthracycline, doxorubicin (DOX), induces NLRP3 inflammasome-dependent IL-1β secretion from murine macrophages. We have also tested several other chemotherapy drugs for their ability to induce IL-1β secretion and/or apoptotic induction in LPS-primed murine bone marrow-derived macrophages (BMDM). Staurosporine (ST), a pro-apoptotic kinase inhibitor, was identified as another rapid inducer of caspase-1 activation and IL-1β release; ST initially (over the first 3 h) activates a K+ efflux-independent casp-1 activation but secondarily engages a K+ efflux-dependent pathway at later (>3h) treatment times. Both DOX and ST also induce rapid (within 1-4 h) accumulation of casp-3/7 activity which coincides with, or precedes, the casp-1 activation and IL-1β secretion responses. Ongoing studies are testing whether: 1) casp-3/7-mediated cleavage of the pannexin-1 channel contributes to the K+ efflux required for NLRP3 inflammasome activation by DOX; and 2) NLRP3-independent inflammasomes mediate the initial K+ efflux-independent IL-1β release elicited by ST.

APA, Harvard, Vancouver, ISO, and other styles

36

Wang, Minan, and Sandra Gollnick. "The mechanisms of photodynamic therapy enhancement of anti-tumor immunity (75.1)." Journal of Immunology 188, no. 1_Supplement (May 1, 2012): 75.1. http://dx.doi.org/10.4049/jimmunol.188.supp.75.1.

Full text

Abstract:

Abstract Photodynamic therapy (PDT) has long been shown to be capable of killing malignant cells and inducing host immune response. Recent investigations have also established that PDT augments anti-tumor immunity. Tumor cells treated by PDT release “danger signals” that have been shown to stimulate dendritic cells (DCs). In this study, we investigate the role of danger signal receptors, specifically the toll-like receptors (TLR) and the NOD-like receptor NLRP3, in PDT generated tumor cell lysates activation of DCs. Stimulation of bone marrow derived DCs (BMDCs) with PDT treated tumor cells leads to dramatic increase in pro-inflammatory cytokine production, including IL-1β, which plays a critical role in PDT efficacy. Production and activation of IL-1β require both TLR and NLR signaling. IL-1β production induced by PDT vaccine in BMDCs is MyD88 dependent. NF-κB is also activated upon treatment of BMDCs with PDT treated tumor cell lysates. Caspase-1, an important component of NLRP3 inflammasome, is known for its role in maturation of IL-1β. However, we found that IL-1β release from DCs is caspase-1 independent. This study aims to understand how PDT enhances tumor immunogenicity and provides insight to improve both in situ PDT and PDT vaccine efficacy in treating secondary disease.

APA, Harvard, Vancouver, ISO, and other styles

37

Ghiringhelli, François, Lionel Apetoh, Antoine Tesniere, Laetitia Aymeric, Yuting Ma, Carla Ortiz, Karim Vermaelen, et al. "Activation of the NLRP3 inflammasome in dendritic cells induces IL-1β–dependent adaptive immunity against tumors." Nature Medicine 15, no. 10 (September 20, 2009): 1170–78. http://dx.doi.org/10.1038/nm.2028.

Full text

APA, Harvard, Vancouver, ISO, and other styles

38

Omosun, Yusuf, Danielle McKeithen, Khamia Ryans, Caroline Kibakaya, Uriel Blas-Machado, Duo Li, Rajesh Singh, et al. "Interleukin-10 Modulates Antigen Presentation by Dendritic Cells through Regulation of NLRP3 Inflammasome Assembly during Chlamydia Infection." Infection and Immunity 83, no. 12 (September 14, 2015): 4662–72. http://dx.doi.org/10.1128/iai.00993-15.

Full text

Abstract:

Interleukin-10 (IL-10) has been implicated in susceptibility to genital chlamydial infection and the development of tubal pathologies. IL-10 limitation also resulted in the rapid elicitation of immune responses againstChlamydia, and decreased levels of IL-10 correlated with protective anti-Chlamydiaimmunity. To investigate the molecular basis for these effects, we compared the reproductive pathologies and fertility rates inChlamydia-infected wild-type (WT) and IL-10-knockout (IL-10−/−) mice; we also analyzed the expression of the Toll-like receptor (TLR)/interleukin-1 receptor (IL-1R) superfamily, IL-1β production, NLRP3 inflammasome assembly and activation, and the immunostimulatory capacity and apoptotic predilection ofChlamydia-exposed dendritic cells (DCs) from WT and IL-10−/−mice. Our results revealed that, in addition to the rapid clearance of infection, genitally infected IL-10−/−mice were protected from tubal pathologies and infertility, whereas WT (IL-10+/+) mice were not.Chlamydia-pulsed IL-10−/−DCs expressed larger numbers of TLR4/IL-1R molecules and had enhanced IL-1β production. In addition, NLRP3 inflammasome assembly was suppressed in IL-10−/−DCs through the inhibition of the P2X purinoceptor 7 (P2X7) receptor (P2X7R), an ATP-gated ion channel, and a decrease in intracellular Ca2+levels, which inhibited DC apoptosis. Thus, the potent immunostimulatory capacity of IL-10-deficient DCs is due, at least in part, to the suppression of the intracellular inflammasome assembly, which prevents DC apoptosis, allowing efficient antigen presentation. The results indicate that IL-10 deficiency enables efficient antigen presentation by DCs for rapid and enhanced immune activation againstChlamydia, which results in rapid microbial clearance, which prevents tubal pathologies during infection. Our finding has important implications for the induction of protective immunity againstChlamydiaand other infectious and noninfectious diseases by vaccines.

APA, Harvard, Vancouver, ISO, and other styles

39

de Melo, Fernando Menegatti, Karine Kawasaki, Tarciso Almeida Sellani, Bruno Souza Bonifácio, Renato Arruda Mortara, Henrique Eisi Toma, Filipe Menegatti de Melo, and Elaine Guadelupe Rodrigues. "Quantum-Dot-Based Iron Oxide Nanoparticles Activate the NLRP3 Inflammasome in Murine Bone Marrow-Derived Dendritic Cells." Nanomaterials 12, no. 18 (September 10, 2022): 3145. http://dx.doi.org/10.3390/nano12183145.

Full text

Abstract:

Inflammasomes are cytosolic complexes composed of a Nod-like receptor, NLR, the adaptor protein, ASC, and a proteolytic enzyme, caspase-1. Inflammasome activation leads to caspase-1 activation and promotes functional maturation of IL-1β and IL-18, two prototypical inflammatory cytokines. Besides, inflammasome activation leads to pyroptosis, an inflammatory type of cell death. Inflammasomes are vital for the host to cope with foreign pathogens or tissue damage. Herein, we show that quantum-dot-based iron oxide nanoparticles, MNP@QD, trigger NLRP3 inflammasome activation and subsequent release of proinflammatory interleukin IL-1β by murine bone marrow-derived dendritic cells (BMDCs). This activation is more pronounced if these cells endocytose the nanoparticles before receiving inflammatory stimulation. MNP@QD was characterized by using imaging techniques like transmission electron microscopy, fluorescence microscopy, and atomic force microscopy, as well as physical and spectroscopical techniques such as fluorescence spectroscopy and powder diffraction. These findings may open the possibility of using the composite MNP@QD as both an imaging and a therapeutic tool.

APA, Harvard, Vancouver, ISO, and other styles

40

Cui, Bin, Jie Sun, Shi-Peng Li, Guang-Peng Zhou, Xiao-Jie Chen, Li-Ying Sun, Lin Wei, and Zhi-Jun Zhu. "CD80+ dendritic cell derived exosomes inhibit CD8+ T cells through down-regulating NLRP3 expression after liver transplantation." International Immunopharmacology 109 (August 2022): 108787. http://dx.doi.org/10.1016/j.intimp.2022.108787.

Full text

APA, Harvard, Vancouver, ISO, and other styles

41

Lawrence, T. M., A. W. Hudacek, M. R. de Zoete, R. A. Flavell, and M. J. Schnell. "Rabies Virus Is Recognized by the NLRP3 Inflammasome and Activates Interleukin-1 Release in Murine Dendritic Cells." Journal of Virology 87, no. 10 (March 13, 2013): 5848–57. http://dx.doi.org/10.1128/jvi.00203-13.

Full text

APA, Harvard, Vancouver, ISO, and other styles

42

Siak, Jay, Anthony St. Leger, Kumarkrishna Raychaudhuri, Mary Mattapallil, Ivan J. Fuss, Raphaela Goldbach-Mansky, Warren Strober, and Rachel R. Caspi. "Commensal microbiota as possible pathobiont in autoinflammatory disease." Journal of Immunology 202, no. 1_Supplement (May 1, 2019): 120.26. http://dx.doi.org/10.4049/jimmunol.202.supp.120.26.

Full text

Abstract:

Abstract The ocular surface has an associated microbiome that contributes to maintenance of local immune homeostasis and protects the ocular surface from fungal and bacterial infections. However, in individuals with a dysregulated immune response, commensal flora could cause pathology. In this study, we seek to understand how an ocular commensal colonizing humans and mice, C. mastitidis (C. mast), stimulates immunity in the immunologically perturbed host. Cryopyrin Associated Periodic Syndrome (CAPS) patients suffer from systemic and ocular autoinflammatory disease caused by a hyperactive NLRP3 inflammasome. Knock-in mice bearing a mutated NLRP3 gene cloned from a CAPS patient responded to ocular colonization with C. mast by increased conjunctival neutrophilia, which progressed to overt ocular surface disease. Compared to wild type (WT) controls, their BM dendritic cells produced elevated IL-1 in response to C. mast. Additionally, gd T cells, which were primarily the Vg4 subset, isolated from eye-draining lymph nodes of C. mast-associated mutant mice were more activated and produced more IL-17, suggesting a qualitatively analogous but quantitatively amplified response compared to WT. Importantly, the same commensal elicited strongly elevated IL-17 production from leukocytes of inflammasome disease patients when compared with healthy controls. Our results suggest that C. mast induces an abnormal immune response in the NLRP3 mutant and acts as a pathobiont, in contrast to its behavior in the immunologically normal host. Based on these data, we hypothesize that the recurrent non-infectious conjunctivitis observed in CAPS patients may be driven by a hyperactive immune response to their own ocular surface bacteria.

APA, Harvard, Vancouver, ISO, and other styles

43

Hara, Hiromitsu, Shinsuke Yasukawa, Masutaka Furue, and Hiroki Yoshida. "IL-1 released by skn dendritic cells activated through Syk and CARD9 pathway is essential for the sensitization of allergic contact dermatitis. (P6245)." Journal of Immunology 190, no. 1_Supplement (May 1, 2013): 181.5. http://dx.doi.org/10.4049/jimmunol.190.supp.181.5.

Full text

Abstract:

Abstract Allergic contact dermatitis (ACD) is caused by T cells reactive to environmental and industrial allergens. Optimal T cell priming requires co-stimulatory signals from DCs that are activated through innate immune sensors. However, innate immune pathways through which contact allergens activate skin DCs are not clear. Here we show that stimulation of contact sensitizers (haptens) induces activation of the tyrosine kinase Syk in DCs. This not only induces the synthesis of pro-IL-1α/β and but also engages the NLRP3 inflammasome, resulting in DC release of IL-1α/β, which is essential for the sensitization of effector T cells. Both CARD9 and MyD88-deficient mice failed to induce contact hypersensitivity (CHS) to haptens. DAP12, Syk and CARD9 were required for hapten-induced IL-1 secretion from DCs, whereas IL-1R1-MyD88 signaling was required in T cells being primed by hapten-activated DCs. The CHS-sensitizing ability of DCs required inflammasome activation that is dependent on ROS generation. The DAP12-Syk signaling was essential for the ROS-regulated inflammasome activation induced by haptens, whereas CARD9/BCL10 signaling selectively controlled pro-IL-1 synthesis by regulating NF-κB activation. Finally, DC-specific deletion of CARD9, DAP12, Syk or NLRP3, but not MyD88 in mice by our newly-developed MixC-Treck system resulted in impaired CHS sensitization. Thus, our results identified an essential molecular axis of innate immunity required for the sensitization of ACD.

APA, Harvard, Vancouver, ISO, and other styles

44

Park, Hyun Jung, Sung Won Lee, Jae Geun Song, Luc Van Kaer, Jae Hee Cheon, Soo-Jeong Lim, Hyo-Kyung Han, and Seokmann Hong. "Aminoclay Nanoparticles Induce Anti-Inflammatory Dendritic Cells to Attenuate LPS-Elicited Pro-Inflammatory Immune Responses." Molecules 27, no. 24 (December 9, 2022): 8743. http://dx.doi.org/10.3390/molecules27248743.

Full text

Abstract:

Although 3-aminopropyl functionalized magnesium phyllosilicate nanoparticles (hereafter aminoclay nanoparticles, ACNs) are well-known nanomaterials employed as drug carriers, their effects on immune cells remain unclear. To address this issue, we explored murine dendritic cells (DCs) as these cells belong to the innate arm of the immune system and function as antigen-presenting cells to elicit adaptive immune responses. We examined the in vitro effects of ACNs on DCs isolated from B6 mice. ACN treatment significantly down-regulated the expression of inflammasome-related markers, including NLRP3, caspase-1, and IL1β. The ACNs-induced anti-inflammatory DC phenotype was further confirmed by down-regulation of the AKT/mTOR/HIF1α signaling pathway. Such anti-inflammatory effects of ACNs on DCs occurred independently of DC subtypes. To document the effects of ACNs on DCs more clearly, we examined their anti-inflammatory effects on lipopolysaccharide (LPS)-activated DCs. As expected, excessive inflammatory responses (increased mitochondrial ROS and Th1-type cytokines such as IL12 and IL1β) of LPS-activated DCs were dramatically attenuated by ACN treatment. Furthermore, ACNs down-regulated IFNγ production by antigen-specific CD4+ T cells, which is consistent with a reduced inflammatory phenotype of DCs. Overall, our results provide support for employing ACNs as drug delivery materials with therapeutic potential to control inflammatory disorders.

APA, Harvard, Vancouver, ISO, and other styles

45

Elmadbouh, Ibrahim, and Dinender K. Singla. "BMP-7 Attenuates Inflammation-Induced Pyroptosis and Improves Cardiac Repair in Diabetic Cardiomyopathy." Cells 10, no. 10 (October 2, 2021): 2640. http://dx.doi.org/10.3390/cells10102640.

Full text

Abstract:

In the present study, we investigated a novel signaling target in diabetic cardiomyopathy where inflammation induces caspase-1-dependent cell death, pyroptosis, involving Nek7-GBP5 activators to activate the NLRP3 inflammasome, destabilizes cardiac structure and neovascularization. Furthermore, we explored the therapeutic ability of bone morphogenetic protein-7 (BMP-7) to attenuate these adverse effects. C57BL/6J mice (n = 16 mice/group) were divided into: control (200 mg/kg, 0.9% saline intraperitoneal injection, i.p.); Streptozotocin (STZ) and STZ-BMP-7 groups (STZ, 200 mg/kg, i.p. injection). After 6 weeks, heart function was examined with echocardiography, and mice were sacrificed. Immunostaining, Western blotting, H&E, and Masson’s trichrome staining was performed on heart tissues. STZ-induced diabetic cardiomyopathy significantly increased inflammasome formation (TLR4, NLRP3, Nek7, and GBP5), pyroptosis markers (caspase-1, IL-1β, and IL-18), inflammatory cytokines (IL-6 and TNF-α), MMP9, and infiltration of monocytes (CD14), macrophage (iNOS), and dendritic cells (CD11b and CD11c) (p < 0.05). Moreover, a significant endothelial progenitor cells (EPCs) dysfunction (c-Kit/FLk-1, CD31), adverse cardiac remodeling, and reduction in left ventricular (LV) heart function were observed in STZ versus control (p < 0.05). Treatment with BMP-7 significantly reduced inflammasome formation, pyroptosis, and inflammatory cytokines and infiltrated inflammatory cells. In addition, BMP-7 treatment enhanced EPC markers and neovascularization and subsequently improved cardiac remodeling in a diabetic heart. Moreover, a significant improvement in LV heart function was achieved after BMP-7 administration relative to diabetic mice (p < 0.05). In conclusion, BMP-7 attenuated inflammation-induced pyroptosis, adverse cardiac remodeling, and improved heart function via the TLR4-NLRP3 inflammasome complex activated by novel signaling Nek7/GBP5. Our BMP-7 pre-clinical studies of mice could have significant potential as a future therapy for diabetic patients.

APA, Harvard, Vancouver, ISO, and other styles

46

de Castro, Lívia Furquim, Larissa Nara Alegrini Longhi, Munir Regini Paião, Amauri da Silva Justo-Júnior, Marcelo Bispo de Jesus, Maria Heloisa de Souza Lima Blotta, and Ronei Luciano Mamoni. "NLRP3 inflammasome is involved in the recognition of Paracoccidioides brasiliensis by human dendritic cells and in the induction of Th17 cells." Journal of Infection 77, no. 2 (August 2018): 137–44. http://dx.doi.org/10.1016/j.jinf.2018.03.004.

Full text

APA, Harvard, Vancouver, ISO, and other styles

47

Hatscher, Lukas, Christian H. K. Lehmann, Ariawan Purbojo, Constantin Onderka, Chunguang Liang, Arndt Hartmann, Robert Cesnjevar, et al. "Select hyperactivating NLRP3 ligands enhance the TH1- and TH17-inducing potential of human type 2 conventional dendritic cells." Science Signaling 14, no. 680 (April 27, 2021): eabe1757. http://dx.doi.org/10.1126/scisignal.abe1757.

Full text

Abstract:

The detection of microorganisms and danger signals by pattern recognition receptors on dendritic cells (DCs) and the consequent formation of inflammasomes are pivotal for initiating protective immune responses. Although the activation of inflammasomes leading to secretion of the cytokine IL-1β is typically accompanied by pyroptosis (an inflammatory form of lytic programmed cell death), some cells can survive and exist in a state of hyperactivation. Here, we found that the conventional type 2 DC (cDC2) subset is the major human DC subset that is transcriptionally and functionally poised for inflammasome formation and response without pyroptosis. When cDC2 were stimulated with ligands that relatively weakly activated the inflammasome, the cells did not enter pyroptosis but instead secreted IL-12 family cytokines and IL-1β. These cytokines induced prominent T helper type 1 (TH1) and TH17 responses that were superior to those seen in response to Toll-like receptor (TLR) stimulation alone or to stronger, classical inflammasome ligands. These findings not only define the human cDC2 subpopulation as a prime target for the treatment of inflammasome-dependent inflammatory diseases but may also inform new approaches for adjuvant and vaccine development.

APA, Harvard, Vancouver, ISO, and other styles

48

Arnold, Isabelle C., Xiaozhou Zhang, Sabine Urban, Mariela Artola-Borán, Markus G. Manz, Karen M. Ottemann, and Anne Müller. "NLRP3 Controls the Development of Gastrointestinal CD11b + Dendritic Cells in the Steady State and during Chronic Bacterial Infection." Cell Reports 21, no. 13 (December 2017): 3860–72. http://dx.doi.org/10.1016/j.celrep.2017.12.015.

Full text

APA, Harvard, Vancouver, ISO, and other styles

49

Mortellaro, Alessandra, Cristina Conforti-Andreoni, Roberto Spreafico, and Paola Ricciardi-Castagnoli. "Uric acid acts as a natural adjuvant by promoting Th17 cell differentiation via an inflammasome-dependent mechanism (176.28)." Journal of Immunology 188, no. 1_Supplement (May 1, 2012): 176.28. http://dx.doi.org/10.4049/jimmunol.188.supp.176.28.

Full text

Abstract:

Abstract Non-microbial molecules released from damaged cells act as natural adjuvants capable of promoting an efficient immune response mediated by innate cells, including macrophages and dendritic cells (DCs). Among these molecules, uric acid (UA) in its crystallized form has been found to trigger inflammation through the activation of NLRP3 inflammasome, which leads to secretion of the proinflammatory cytokines IL-1β and IL-18. UA modulation of innate immune responses has been extensively studied, but the impact of this damage-associated molecular pattern on adaptive responses remains largely undocumented. As one of the most ubiquitous sterile danger signals in mammals, and in view of the key role played by UA in alum adjuvanticity, we sought to determine how UA crystals shape adaptive immune responses. In the present study, we focused on adaptive CD4+ T cell polarization since adjuvants that are able to direct appropriately polarized responses will be key to the success of next-generation vaccination strategies. In the presence of NF-κB signaling delivered by muramyl dipeptide, UA crystals were capable of stimulating DCs to promote the release of cytokines associated with Th17 polarization. Accordingly, UA crystals potently induced Th17 responses both in vitro and in vivo. These effects were dependent on the inflammasome-related cytokines IL-1α/β and IL-18, as well as on ASC and caspase-1. Accordingly, NLRP3 deficiency significantly impaired Th17 polarization, at least in vitro.

APA, Harvard, Vancouver, ISO, and other styles

50

Bauer, David Laurence, Jonathan R. Kurtz, Samuel B. Grant, Vicki E. Immethun, and James B. McLachlan. "Adjuvant combinations activate dendritic cells and contribute to antigen-specific CD4 T cell expansion." Journal of Immunology 204, no. 1_Supplement (May 1, 2020): 166.15. http://dx.doi.org/10.4049/jimmunol.204.supp.166.15.

Full text

Abstract:

Abstract Adjuvants are important mediators of immune responses and enhance the activation of innate immune cells, leading to protective T and B cell responses. Only a few vaccine adjuvants are currently approved for use in the US and, along with the discovery of novel adjuvants, combination adjuvants are likely to have a major impact on future vaccine development. Here, we investigated the ability of both the double mutant Escherichia coli heat labile toxin R192/L211A (dmLT) and the TLR4 agonist monophosphoryl lipid A (MPL-A) to drive innate and adaptative immune responses independently and in combination. We found that the combination adjuvant induces more robust activation of dendritic cells (DCs) than either adjuvant alone, leading to the formation of the NLRP3 inflammasome complex and increased secretion of IL-1β, as well as other hallmark pro-inflammatory cytokines. Furthermore, RNA sequencing and ingenuity pathway analysis support that the combination adjuvant may allow these DCs to polarize a multi-faceted Th1/2/17 CD4 T cell response. To determine how this adjuvant combination might regulate CD4 T cell responses, we intradermally immunized mice with a model T cell antigen in conjunction with dmLT or MPL-A alone or combined and, using MHC class II tetramers, found that vaccination with the combination demonstrated the greatest expansion and activation of endogenous, vaccine-specific CD4+ T cells in all lymphoid tissues assessed which included a Th1/Th17 response. These results reveal how combination adjuvants can be used to not only potentiate better vaccine responses, but to potentially bias the immune response to one that is more capable of combating infection.

APA, Harvard, Vancouver, ISO, and other styles

Journal articles on the topic 'Dendritic cells NLRP3'

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles