Добірка наукової літератури з теми "Mybacterium tuberculosis - Inflammatory Response"

Summary The main issue in patients with pulmonary tuberculosis (PTB) represents the impossibility of the host immune response to express bactericidal function and the sterilization of lesions depends exclusively on the specific antimicrobial chemotherapy. In order to investigate the value of acute-phase inflammatory response markers in patients with newly confirmed extensive PTB, there was designed a clinical study with 80 patients, of whom 40 had active disease (experimental group), while other 40 had inactive sequellar disease without comorbidity (control group). The examined groups were homogenous with respect to the patient’s general demographic characteristics. In the experimental group, 20.0% of the patients had an initial bacterial infection of the lower respiratory tract, while their average value of acute-phase systemic inflammatory markers was initially, before the antituberculosis treatment, significantly elevated compared to the control group. At the end of the treatment, values of erythrocyte sedimentation rate in the first hour (SE) and serum C-reactive protein (CRP) significantly decreased (SE-p <0.001, CRP-p<0.001), together with the value of the leukocyte count (Le) and serum fibrinogen (Le-p<0.001, fibrinogen-p<0.001). Multivariate linear regression analysis proved a significant correlation between baseline serum fibrinogen level with positive history of contact with active TB patient and initial radiological extent of PTB lung lesions. The values of the acute-phase inflammatory response markers in active PTB have its clinical significance in the assessment of unfavourable course of disease in extensive disseminated form of PTB as well as in the occurrence of complications associated with low respiratory tract bacterial superinfection.

Mycobacterium tuberculosis and cancer are two diseases with proclivity for the development of resistance to the host immune system. Mechanisms behind resistance can be host derived or disease mediated, but they usually depend on the balance of pro-inflammatory to anti-inflammatory immune signals. Immunotherapies have been the focus of efforts to shift that balance and drive the response required for diseases eradication. The immune response to tuberculosis has widely been thought to be T cell dependent, with the majority of research focused on T cell responses. However, the past decade has seen greater recognition of the importance of the innate immune response, highlighting factors such as trained innate immunity and macrophage polarization to mycobacterial clearance. At the same time, there has been a renaissance of immunotherapy treatments for cancer since the first checkpoint inhibitor passed clinical trials, in addition to work highlighting the importance of innate immune responses to cancer. However, there is still much to learn about host-derived responses and the development of resistance to new cancer therapies. This review examines the similarities between the immune responses to cancer and tuberculosis with the hope that their commonalities will facilitate research collaboration and discovery.

ABSTRACT Tuberculosis leads to immune activation and increased human immunodeficiency virus type 1 (HIV-1) replication in the lung. However, in vitro models of mycobacterial infection of human macrophages do not fully reproduce these in vivo observations, suggesting that there are additional host factors. Surfactant protein A (SP-A) is an important mediator of innate immunity in the lung. SP-A levels were assayed in the human lung by using bronchoalveolar lavage (BAL). There was a threefold reduction in SP-A levels during tuberculosis only in the radiographically involved lung segments, and the levels returned to normal after 1 month of treatment. The SP-A levels were inversely correlated with the percentage of neutrophils in BAL fluid, suggesting that low SP-A levels were associated with increased inflammation in the lung. Differentiated THP-1 macrophages were used to test the effect of decreasing SP-A levels on immune function. In the absence of infection with Mycobacterium tuberculosis, SP-A at doses ranging from 5 to 0.01 μg/ml inhibited both interleukin-6 (IL-6) production and HIV-1 long terminal repeat (LTR) activity. In macrophages infected with M. tuberculosis, SP-A augmented both IL-6 production and HIV-1 LTR activity. To better understand the effect of SP-A, we measured expression of CAAT/enhancer binding protein beta (C/EBPβ), a transcription factor central to the regulation of IL-6 and the HIV-1 LTR. In macrophages infected with M. tuberculosis, SP-A reduced expression of a dominant negative isoform of C/EBPβ. These data suggest that SP-A has pleiotropic effects even at the low concentrations found in tuberculosis patients. This protein augments inflammation in the presence of infection and inhibits inflammation in uninfected macrophages, protecting uninvolved lung segments from the deleterious effects of inflammation.

We present a case of a 39-year-old male patient with Acquired Immune Deficiency Syndrome (AIDS) who developed Mycobacterium tuberculosis related Immune Reconstitution Inflammatory Syndrome (IRIS) after initiation of Highly Active Antiretroviral Therapy (HAART) treatment. The inflammatory response resulted in mediastinal necrotic lymphadenopathy and subsequent perforation of the esophageal wall.

We present a case of a 39-year-old male patient with Acquired Immune Deficiency Syndrome (AIDS) who developed Mycobacterium tuberculosis related Immune Reconstitution Inflammatory Syndrome (IRIS) after initiation of Highly Active Antiretroviral Therapy (HAART) treatment. The inflammatory response resulted in mediastinal necrotic lymphadenopathy and subsequent perforation of the esophageal wall.

OBJECTIVE: To describe serum levels of the cytokines IL-10, TNF-α, and IFN-γ, as well as polymorphisms in the genes involved in their transcription, and their association with markers of the acute inflammatory response in patients with pulmonary tuberculosis.METHODS: This was a descriptive, longitudinal study involving 81 patients with pulmonary tuberculosis treated at two referral hospitals. We collected data on sociodemographic variables and evaluated bacteriological conversion at the eighth week of antituberculosis treatment, gene polymorphisms related to the cytokines studied, and serum levels of those cytokines, as well as those of C-reactive protein (CRP). We also determined the ESR and CD4+ counts.RESULTS: The median age of the patients was 43 years; 67 patients (82.7%) were male; and 8 patients (9.9%) were infected with HIV. The ESR was highest in the patients with high IFN-γ levels and low IL-10 levels. IFN-γ and TNF-α gene polymorphisms at positions +874 and −238, respectively, showed no correlations with the corresponding cytokine serum levels. Low IL-10 levels were associated with IL-10 gene polymorphisms at positions −592 and −819 (but not −1082). There was a negative association between bacteriological conversion at the eighth week of treatment and CRP levels.CONCLUSIONS: Our results suggest that genetic markers and markers of acute inflammatory response are useful in predicting the response to antituberculosis treatment.

Platelets play a special role in the systemic inflammatory response syndrome, as they acquire the ability to become activated and aggregate. Literature has no direct evidence of a link between platelet aggregation activity and the severity of the systemic inflammatory response syndrome in patients with pulmonary tuberculosis. The aim of the paper is to study platelet aggregation in patients with pulmonary tuberculosis with severe systemic inflammatory response syndrome. Materials and Methods. Spontaneous and induced by ADP (0.1, 1.0 and 5.0 ml) platelet aggregation was determined by Born turbodynamic method. The study enrolled 27 patients with severe and 33 patients with indolent systemic inflammatory response syndrome Spontaneous and induced by ADP (0.1 and 1.0 ml) platelet aggregation was evaluated in absorbance units (a.u.); platelet aggregation induced by 5.0 ml of ADP was measured in percentage terms. Statistica 10 was used to process the results. Discrepancy tests were used to determine the significance of differences of mean values; McNemar’s test and Fisher’s exact test were used to estimate event rate, p<0.05. Results. In Group 1 spontaneous and induced by ADP (0.1, 1.0 and 5 ml) platelet aggregation was 0.85–2.65 (1.210.1) a.u., 0.81–3.67 (3.030.38) a.u., 1.06–6.25 (6.50.51) a.u., 5–66 % (39.53.6); in Group 2 – 0.84–1.36 (1.10.04) a.u., 0.77–2.49 (2.10.26) a.u., 0.64–5.49 (2.200.08) a.u., 8–66 (35.74.14) %, respectively. Frequency of spontaneous and induced by ADP (0.1, 1.0 and 5 ml) platelet hypoaggregation in Groups 1 and 2 was 33.3 % and 27.3 %; 14.8 % and 24.2 %; 0 % and 39.4 %; 14.8 % and 24.2 %, respectively; frequency of hyperaggregation was 14.8 % and 0 %; 11.1 % and 9.1 %; 29.6 % and 0 %; 0 % and 0 %, respectively. Conclusion. Platelet aggregation activity in patients with pulmonary tuberculosis is determined by the severity of the systemic inflammatory response syndrome. A pronounced systemic inflammatory response syndrome is associated with increased spontaneous and induced by ADP (1.0 ml) platelet aggregation in 14.8 % and 29.6 % of cases, respectively.

SUMMARY The different manifestations of infection with Mycobacterium tuberculosis reflect the balance between the bacillus and host defense mechanisms. Traditionally, protective immunity to tuberculosis has been ascribed to T-cell-mediated immunity, with CD4+ T cells playing a crucial role. Recent immunological and genetic studies support the long-standing notion that innate immunity is also relevant in tuberculosis. In this review, emphasis is on these natural, innate host defense mechanisms, referring to experimental data (e.g., studies in gene knockout mice) and epidemiological, immunological, and genetic studies in human tuberculosis. The first step in the innate host defense is cellular uptake of M. tuberculosis, which involves different cellular receptors and humoral factors. Toll-like receptors seem to play a crucial role in immune recognition of M. tuberculosis, which is the next step. The subsequent inflammatory response is regulated by production of pro- and anti-inflammatory cytokines and chemokines. Different natural effector mechanisms for killing of M. tuberculosis have now been identified. Finally, the innate host response is necessary for induction of adaptive immunity to M. tuberculosis. These basic mechanisms augment our understanding of disease pathogenesis and clinical course and will be of help in designing adjunctive treatment strategies.

ABSTRACT To investigate the role of chemokines during the initial local response to Mycobacterium tuberculosis in the human lung, we studied chemokine production by the human alveolar epithelial cell line A549 after infection with M. tuberculosis. M. tuberculosis-infected A549 cells produced mRNAs and protein for monocyte chemotactic protein-1 (MCP-1) and interleukin-8 (IL-8) but not mRNAs for macrophage inflammatory protein 1α (MIP-1α), MIP-1β, and RANTES. Chemokine production in response to M. tuberculosis was not dependent on production of tumor necrosis factor alpha, IL-1β, or IL-6. Two virulent clinical M. tuberculosis isolates, the virulent laboratory strain H37Rv, and the avirulent strain H37Ra elicited production of comparable concentrations of MCP-1 and IL-8, whereas killed M. tuberculosis and three Mycobacterium avium strains did not. The three virulent M. tuberculosis strains grew more rapidly than the avirulent M. tuberculosisstrain in the alveolar epithelial cell line, and the threeM. avium strains did not grow intracellularly. These findings suggest that intracellular growth is necessary for mycobacteria to elicit production of MCP-1 and IL-8 by alveolar epithelial cells but that virulence and the rate of intracellular growth do not correlate with chemokine production. Alveolar epithelial cells may contribute to the local inflammatory response in human tuberculosis by producing chemokines which attract monocytes, lymphocytes, and polymorphonuclear cells.

The mammalian immune system consists of the innate and adaptive arm/s that protect the host against pathogenic infections in a highly coordinated process involving multiple steps. Innate immune cells such as macrophages and dendritic cells (DCs) are responsible for determining the initiation of specific events and thus they tailor specific immune responses to eliminate the invading pathogen. Host innate immune responses are triggered by sensing of PAMPs (pathogen associated molecular patterns) or DAMPs (damage associated molecular patterns) via pattern recognition receptors (PRRs) and these inturn facilitate adaptive immune responses. The four major families of PRRs including Toll- like receptors (TLRs), NOD-like receptors (NLRs), RIG-I like receptors (RLRs) and C-type lectin receptors (CLRs) recognize a wide range of PAMPs and DAMPs. Engagement of PRRs with these stimuli promotes the differential induction of PRRs-driven signaling cascades such as inflammation, apoptosis, and autophagy among others that result in organized actions of multiple immune cells to eradicate microbial infection. However, in spite of having such effective and efficient immune system, some of the pathogens are able to breach immune layers and establish a successful infection while escaping host key immune surveillance mechanisms. One such pathogen of rising concern, Mycobacterium tuberculosis (Mtb) causing tuberculosis (TB), has evolved with mankind and causes an alarming 1.4 million deaths annually, in accordance with recent WHO reports. Mtb is an intracellular pathogen, whose primary target cells are macrophages. These are crucial effector immune cells that provide defense against a vast array of pathogens through the presentation of abundant cell surface receptors including TLRs that sensitize the host and execute the tailoring of immune responses during mycobacterial infection. In particular, TLR2 has been shown to elicit inflammatory responses including the increased expression of effector molecules such as tumor necrosis factor (TNF) α, interferon gamma (IFN-γ), xiinterleukins (ILs), chemokines and inflammatory cytokines in this process. Accumulating evidences indicate the role of phagosomal nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX)2 in producing oxidative stress in order to clear pathogen. Recent reports have suggested essential role of NOX2 in efficient killing of mycobacteria. For example, p47-phox (NOX2 subunit) null mouse showed increased susceptibility to mycobacteria infection. Interestingly, another recent study suggested the crucial role of host NAD(P)H quinone oxidoreductase 1 (NQO1) in promoting mycobacterial survival. Yet the contribution of NQO1 in regulating immune responses during pathogenic mycobacteria infection needs further investigation. Additionally, few reports indicate the role for hostderived reductases in regulating apoptosis. More importantly, several studies propose that mycobacteria can inhibit apoptosis and promote its survival. Therefore, dissecting the molecular mechanism in regulating host-derived reductases during mycobacterial infection will provide a further insight into comprehending the success of Mtb infection which depends on its ability to evade host immune responses by modulating host signaling and the related expression of immuno-regulatory molecules. In line with the above observations, defined signaling downstream of TLRs plays a central role in generating effective immune responses at the site of infection. Several immunological modules act as important accessory events to TLR-triggered signaling. Among the many signaling pathways, the canonical WNT-β-catenin pathway has been recently shown to play a crucial role in controlling the expression of inflammatory molecules during infection. However, information on the roles of WNT signaling in mediating inflammatory responses remains scanty. In particular, a growing number of studies have indicated the potential involvement of epigenetic factors to determine the host cell inflammatory responses. Modifications by such factors including DNA methylation, histone modification and noncoding RNAs are shown to be potential regulators of TLR mediated inflammatory responses. Histone methylation plays a crucial role in mediating TLR-triggered immune responses. For example, H3K27 demethylase Jumonji domain-containing 3 (JMJD3) was shown to determine the M2 macrophage development upon TLR stimulation during helminth infection. Furthermore, methyltransferases including SETDB2 and ASH1L, repress the expression of CXC-chemokine ligand 1 (CXCL1) and LPS-induced production of inflammatory cytokines respectively. However, it has not yet been determined, how pathogen modulates the recruitment of these epigenetic modifiers at specific promoters, thus orchestrating changes in complex phenomena such as inflammatory responses and apoptosis. Based on these evidences, the former part of the present study is focused on the expression of WNT-responsive epigenetic effectors which mediate the inflammatory responses and apoptosis during mycobacterial infection in mice. The investigation demonstrates that Mtb H37Rv triggers a robust activation of WNT-β-catenin signaling via its adaptor molecule protein kinase C (PKC) ζ. Indeed, emerging studies suggest a potential contribution of miRNAs in modulating immune responses during pathogenic infection. In line with these observations, we show that the WNT-responsive Mir-30e-3p stabilizes H4K20me1 methyltransferase SET8 by modulating the expression of its negative regulator, CDT2 (E3 ubiquitin ligase) during mycobacterial infection. Notably, stabilised SET8 leads to increased monomethylation of H4K20 on the promotors of Nqo1 and Trxrn1, which reflects in their significantly high RNA and protein levels. Despite being bonafide antioxidants, NQO1 is known to play a crucial role in regulating inflammation and TRXR1 is considered as an apoptosis controller via the regulation of ASK1 activity. Thus the depletion of NQO1 and TRXR1 by using specific siRNA reveals the important roles for NQO1 and TRXR1 in regulating inflammatory responses and apoptosis respectively during mycobacterial infection. Furthermore, experiments based on the use of dicoumarol (NQO1 inhibitor) and auranofin (TRXR1 inhibitor) in macrophages followed by pathogenic mycobacterial infection suggested that inflammatory responses and apoptosis are dependent on reductase activity of NQO1 and TRXR1. Most importantly, these functions of TRXR1 and NQO1 were explored in an experimental mouse TB model. Interestingly, mice administered with dicoumarol and auranofin showed a significantly reduced lung and spleen Mtb CFU. This was also corroborated by lung histopathology which alluded the reduced severity of TB through the analysis of granuloma, underscoring the importance of NQO1 and TRXR1 in TB pathogenesis. Collectively, we suggest the crucial role for WNT-responsive Mir-30e-3p - histone methyltransferase SET8 axis in regulating host-derived antioxidants NQO1 and TRXR1 in suppressing host immune responses. Thus, epigenetic reprogramming of the host cell by SET8 promotes Mtb survival in macrophages by regulating inflammation and apoptosis. Additionally, another histone methyltransferase, ASH2L, has been established as an immune regulator via facilitating activatory H3K4me3 (trimethylation) on the promoters of target genes at CG-rich DNA motifs. The participation of H3K4me3 performed by ASH2L methyltransferase, is highlighted in regulation of immune-related genes. However contribution of AHS2L in regulating host immune responses during mycobacterial infection has been not addressed. Based on these evidences, we established that Mtb-induced ASH2L, coupled with β-catenin directly regulates the expression of 5-LO and 15-LO. As a functional consequence, WNT/β-catenin and its responsive 5-LO and 15-LO were found to regulate expression of Gpr18 transcript which in turn regulates host inflammatory responses. In addition to membrane bound TLRs, emerging studies suggest the effective role for cytosolic NLRs in sensing PAMPs or DAMPs with great efficiency. Among the NLRs, nucleotide-binding oligomerization domain-containing protein (NOD) 1 and NOD2 are well characterized cytosolic receptors in determining inflammatory responses. Although, inflammation is a highly regulated fundamental defensive host mechanism, its hyper and chronic activation in response to different stimuli is associated with serious inflammatory disorders. Importantly, recent reports implicated the close association of NOD2 and WNT signaling pathways during the development of Crohn’s disease. In continuation, evidence suggests that NOD2-driven inflammatory disorders are associated with impairment of inflammasome function. Activation of WNT signaling is also implicated in the development of arthritis. However, precise mechanism of NOD2-WNT-inflammasome crosstalk or the pivotal role of WNT signaling during inflammatory arthritis requires extensive investigation. In this context, the present investigation demonstrates that upon activation with muramyl dipeptide (MDP, NOD2 specific agonist), NOD2 interacts positive regulator of WNT signaling Ly6/PLAUR domain-containing protein 6 (LYPD6) to stimulate and mediate WNT signaling activation. Strikingly, canonical adaptor molecules of NOD2 signaling, RIP2 and TAK1 were proven to be dispensable in NOD2-triggered WNT signaling activation. Furthermore, we found that WNT-responsive X-linked inhibitor of apoptosis (XIAP) leads to activation of NOD like receptors family pyrin domain-containing 3 (NLRP3) inflammasome complex. Further, NOD2-stimulated formation of active caspase-1 and secretion of IL-1β were found to be dependent on WNT and its responsive XIAP. Consistent with this in vitro data, mice administered with WNT-signaling inhibitor, XIAP inhibitor or Caspase-1 inhibitor displayed compromised ability to develop MDP-triggered acute arthritis. Taken together, our study contributes new biological insights towards understanding of NOD2-associated inflammatory responses. Altogether, our findings lay the groundworks for comprehending conceptual framework in orchestrating TLR and NLR responses by WNT/β-catenin signaling. More importantly, our study pays a tribute to novel mechanistic and functional insights into Mtb pathogenesis and inflammatory diseases, which promises to provide important leads in diagnostic and therapeutic approaches for immune-associated disorder

This chapter covers two case studies and scenarios: a case of pulmonary tuberculosis (TB) in a college student; and a case of laboratory-confirmed Mycobacterium bovis in an adult with inflammatory bowel disease. The pulmonary TB case resulted in a wider investigation and contact tracing as the case attended college while symptomatic. The Mycobacterium bovis resulted in wider workplace and hospital contact tracing through convening an Incident Control Team. Background information on the epidemiology and clinical features of TB and the public health response to TB in educational, healthcare, and occupational settings are discussed. Case definitions, and a detailed risk assessment, with clear description of close contacts, priority groups, and the required public health actions, are described. ‘Top tips’ are given, to provide practical tips for the reader to think through the public health management of TB, and ‘tools of the trade’ list the laboratory and epidemiological components of the investigation.

Mitochondria are multifunctional organelles that actively participate in the immune-inflammatory response in various pathologies. This volume updates readers on knowledge about mitochondria function. The editors have compiled six chapters about inflammation in its broadest sense, with contributions from active groups of cell biologists, infectologists and pathologists. The chapters in this volume focus on research related to five notable diseases: (1) two diseases (one bacterial and one viral) in which the exacerbation of the inflammatory response can lead to neuropathies: leprosy (one of the oldest diseases in the world) and Zika fever (a disease relatively new in Brazil) (2) three diseases (two bacterial and one viral) in which the exacerbation of the inflammatory response can lead to irreversible lung damage that can cause rapid death: tuberculosis, pneumonia and the most recent global disease, COVID- 19. New information about mitochondrial biology is presented, such as the effect of aerobic physical exercise as a stimulator for mitochondria multiplication, and the role of mitochondrial damage in inducing immune-inflammatory responses to pathogens. The contents shed light on mitochondrial biochemical pathways that could serve as potential therapeutic targets. This is an important reference for scholars (cell biologists, microbiologists) in universities, hospitals and scientific research centers working on biological and biomedical problems, and for health professionals involved in infection control.

Panniculitis is an inflammation that originates primarily in the subcutaneous fatty tissue (panniculus adiposus). It is associated with rheumatological diseases and with adverse events to rheumatological therapies (e.g. poststeroid panniculitis, erythema nodosum, infective panniculitis). The panniculitides are classified histopathologically into mostly septal panniculitis and mostly lobular panniculitis, according to the major or denser localization of the infiltrate, and also into those with or without vasculitis. Additional criteria involve the composition of the inflammatory infiltrate, the cause, and an underlying or associated disease. The clinical hallmarks of panniculitis are subcutaneous nodules or plaques, often located on the lower limb. A deep excisional biopsy is often required for a more precise diagnosis, given the often sparse and monotonous clinical symptoms. Erythema nodosum is the most common form and a typical example of septal panniculitis. It occurs in response to many different provoking factors, the most common trigger in children being a 'strep throat', in adults sarcoidosis. Clinically, it presents with a sudden symmetrical appearance of painful, tender, warm, erythematous nodes or plaques, usually on the shins, which resemble bruises. Classical and cutaneous polyarteriitis nodosa present a mostly septal panniculitis associated with vasculitis. Here subcutaneous, partially ulcerating nodules are surrounded by livedo racemosa. The mostly lobular panniculitides not associated with vasculitis include lupus panniculitis (lupus erythematosus profundus, typically with ensuing lipoatrophy and predilection for the upper part of the body), panniculitis in dermatomyositis (often calcifiying), cold panniculitis, pancreatic panniculitis, panniculitis due toα‎-antitrypsin deficiency, poststeroid panniculitis (in children after rapid withdrawal of corticosteroids), calciphylaxis (with and without renal failure), and factitious panniculitis (after mechanical, physical, or chemical injuries to the subcutaneous tissue, often self-inflicted). Nodular vasculitis (formerly erythema induratum Bazin) is a lobular panniculitis with vasculitis involving mostly the small blood vessels of the fat lobule. It appears to present a (hyper)reactive response to certain infections (tuberculosis, streptococci, candida) or to cold exposure or chronic venous insufficiency in susceptible females. In conclusion, the panniculitides are a heterogenous group of diseases requiring a systematic work-up and knowledge of certain histological or clinical criteria.

Tuberculosis (TB) is a contagious infectious disease that is a major cause of morbidity, being one of the top 10 causes of death worldwide, and the leading one from a single infectious agent. Also called “White Plague” in the past, TB is an airborne disease, propagated when multibacillary people spread M. tuberculosis by coughing or sneezing. The disease typically affects the lungs (pulmonary TB), but can also affect other sites (extrapulmonary TB). TB is curable and preventable: about 85% of the people who develop the disease may be successfully treated with a 6-month multidrug regimen. The treatment has the additional benefit of preventing onward transmission. Macrophages are the first host cell to get in contact with M. tuberculosis. They also have important effector functions, regardless of whether the infection evolves to a chronic or latent form. However, M. tuberculosis evades host cell innate defense mechanisms, manipulates organelles and cell metabolism, as well as host cell death pathways. This complex interaction between the host cell and the bacillus determines the outcome of the infection. In this context, mitochondria and mitochondrial DNA (mtDNA) contribute to triggering cell death by necrosis. However, excessive necrosis may lead to tissue damage, which disrupts granulomas and benefits M. tuberculosis transmission. We intend to revisit the major aspects of this intricated and multifaceted interface between the host immune cell and M. tuberculosis and discuss how mitochondria are the crux of the matter

Mitochondria are highly relevant organelles with regard to their unique function in generating energy and contributing to metabolism within the cell. Furthermore, recent studies suggest that they might have an influence on the innate immune and inflammatory responses, thus affecting antiviral immunity (as example: Zika virus (ZIKV), hepatitis C virus (HCV), dengue virus and SARS-CoV-2 virus) and antibacterial immunity as well (Streptococcus pneumoniae, Mycobacterium leprae and Mycobacterium tuberculosis). Therefore, this chapter aims at bringing a relevant debate about the role of mitochondria and their multifunctional capacity. We intend to discuss the complexity of mitochondrial metabolism, especially during aerobic physical exercises, which causes the modulation of the gene expression of proteins that lead to mitochondrial proliferation and, thus, promote health. In addition, considering the injuries caused by hypoxia, this chapter also stresses the enormous potential of mitochondria to enable the survival of eukaryotic cells by allowing them to turn to aerobic respiration, as shown in previous scientific studies. In conclusion, this chapter points out the importance of mitochondrial biogenesis (both natural and stimulated biogenesis by aerobic exercise) and the benefits this organelle brings to the health, arguing that they go far beyond cellular respiration and oxidative phosphorylation.

Viral and idiopathic pericarditis are the most common forms of pericarditis encountered in clinical practice in developed countries with a low prevalence of tuberculosis. The course of these cases is relatively benign and self-limiting, the most common complication being recurrence. The mainstay of therapy is empiric anti-inflammatory therapy with aspirin or a non-steroidal anti-inflammatory drug (NSAID) plus colchicine. Specific features at presentation may suggest the increased risk of complications during follow-up and non-viral aetiologies (e.g. high fever >38ºC (100.4ºF), subacute course with symptoms over several days without a clear-cut acute onset, evidence of large pericardial effusion with diastolic echo-free space >20 mm, cardiac tamponade, failure to respond within 7 days to aspirin/NSAID, associated myocarditis (myopericarditis), immunodepression, trauma, and oral anticoagulant therapy). The presence of one or more of these features identifies a potentially high-risk case of pericarditis to be admitted. In these cases an aetiology search is mandatory. Patients with pericarditis and no risk features can be considered at low risk and managed as outpatients. In these cases follow-up is mandatory after 1 week to assess the response to empiric anti-inflammatory therapy. Recurrent pericarditis is the most troublesome complication following acute pericarditis and occurs in 20–50% of patients. Most cases of recurrent pericarditis are idiopathic and the pathogenesis is presumed to be immune mediated or autoinflammatory. The prognosis of idiopathic recurrent pericarditis is generally good with the risk of chronic evolution towards constrictive pericarditis related to the aetiology and not the number of recurrences.

Sarcoidosis is a benign systemic granulomatous pathology of unknown etiology. Mammary involvement is rare, less than 1% of all cases. That is the reason that makes necessary an optimal differential diagnosis to rule out malignant pathology as the main diagnosis. Imaging tests such as mammography, ultrasound, or MRI contribute to the diagnosis but are unable to establish a certain diagnosis. When a mammary sarcoidosis is suspected by fine needle aspiration cytology, exceptional procedures are necessary to confirm the disease and to exclude a coexisting carcinoma. Malignancy may develop in patients with sarcoidosis, sarcoidosis may develop in patients with breast cancer, the two diseases may develop in tandem, or breast cancer may cause a sarcoidosis-like granulomatous response. Other illnesses that should rule out are granulomatous diseases, which could be differentiated into infectious causes such as tuberculosis and primary inflammatory diseases such as idiopathic granulomatous mastitis. The silicone of gel breast implants may originate a sarcoidosis-like reaction as the result of an acceleration of an already existing hypersensitivity response, resulting in breast sarcoidosis. The management of sarcoidosis in the breast is usually enough with an excisional biopsy. The prognosis of mammary sarcoidosis in not unknown.

You need to ensure that you are not mistaking haemoptysis with: • Haematemesis: brownish-red blood that is vomited from the gastrointestinal (GI) tract. • Epistaxis (nosebleed): particularly a posterior nosebleed. • Bleeding gums: combined with a cough, this may be confused with true haemoptysis. To tell if it is really haemoptysis, you can ask the patient where they think the blood is coming from (they may say it initially dripped from their nose), its colour (darker, coffee-ground appearance suggests partially digested blood), any history of nosebleeds, nausea, vomiting, gastric disease, or alcoholism. For the latter, asking if he is an alcoholic is unlikely to yield a valid response. Instead, you can try the TACE questions to detect alcohol dependence: . . . Does it Take more than three drinks to make you feel high? Have you ever been Annoyed by people’s criticism of your drinking? Are you trying to Cut down on drinking? Have you ever used alcohol as an Eye-opener in the morning? A positive response to the first question scores 2 points and a positive response to each of the rest, scores 1 point each. A positive response to two of these four questions is considered to indicate possible alcohol abuse or dependence as does a total score of two or more points. Haemoptysis should always be investigated thoroughly for two reasons: 1 It may be the presenting symptom for life-threatening lung disease. 2 Massive haemoptysis, variably defined as anything from >100 mL to >1000 mL over 24 hours, may be life-threatening itself, usually through asphyxiation but potentially also shock. Haemoptysis is thus a ‘red flag’ symptom and any patient with haemoptysis requires a thorough diagnostic work-up. These can be grouped together under a ‘surgical sieve’—we have used INVITED MD: Infective: pulmonary tuberculosis (TB), bronchitis, pneumonia, lung abscess, mycetoma Neoplastic: primary lung cancer, metastatic lung cancer Vascular: pulmonary embolism, left ventricular failure, bleeding diathesis (i.e. a bleeding tendency e.g. coagulopathy, severe thrombocytopenia), arteriovenous malformation, vascular–bronchial fistula Inflammatory: granulomatosis with polyangiitis (formerly called Wegener’s granulomatosis), Goodpasture’s syndrome, systemic lupus erythematosus, hereditary haemorrhagic telangiectasia (Osler–Weber–Rendu syndrome), polyarteritis nodosa, microscopic polyangiitis

Panniculitis is an inflammation that originates primarily in the subcutaneous fatty tissue (panniculus adiposus). It is associated with rheumatological diseases and with adverse events to rheumatological therapies (e.g. poststeroid panniculitis, erythema nodosum, infective panniculitis). The panniculitides are classified histopathologically into mostly septal panniculitis and mostly lobular panniculitis, according to the major or denser localization of the infiltrate, and also into those with or without vasculitis. Additional criteria involve the composition of the inflammatory infiltrate, the cause, and an underlying or associated disease. The clinical hallmarks of panniculitis are subcutaneous nodules or plaques, often located on the lower limb. A deep excisional biopsy is often required for a more precise diagnosis, given the often sparse and monotonous clinical symptoms. Erythema nodosum is the most common form and a typical example of septal panniculitis. It occurs in response to many different provoking factors, the most common trigger in children being a ’strep throat’, in adults sarcoidosis. Clinically, it presents with a sudden symmetrical appearance of painful, tender, warm, erythematous nodes or plaques, usually on the shins, which resemble bruises. Classical and cutaneous polyarteriitis nodosa present a mostly septal panniculitis associated with vasculitis. Here subcutaneous, partially ulcerating nodules are surrounded by livedo racemosa. The mostly lobular panniculitides not associated with vasculitis include lupus panniculitis (lupus erythematosus profundus, typically with ensuing lipoatrophy and predilection for the upper part of the body), panniculitis in dermatomyositis (often calcifiying), cold panniculitis, pancreatic panniculitis, panniculitis due toα‎‎-antitrypsin deficiency, poststeroid panniculitis (in children after rapid withdrawal of corticosteroids), calciphylaxis (with and without renal failure), and factitious panniculitis (after mechanical, physical, or chemical injuries to the subcutaneous tissue, often self-inflicted). Nodular vasculitis (formerly erythema induratum Bazin) is a lobular panniculitis with vasculitis involving mostly the small blood vessels of the fat lobule. It appears to present a (hyper)reactive response to certain infections (tuberculosis, streptococci, candida) or to cold exposure or chronic venous insufficiency in susceptible females. In conclusion, the panniculitides are a heterogenous group of diseases requiring a systematic work-up and knowledge of certain histological or clinical criteria.

Primary breast tuberculosis is a rare extrapulmonary tuberculosis mainly affecting young women of childbearing age in endemic countries. Its incidence is increasing in immunocompromized and HIV-infected people and with the emergence of drug-resistant strains of Mycobacterium tuberculosis. There are no specific clinical signs suggestive of this disease, and it often presents as a hard mass or breast abscess. There is an overlap of features with other inflammatory, infectious, benign lesions, fat necrosis, and malignant neoplasms of the breast. The detection of Mycobacterium tuberculosis remains the gold standard for diagnosis. Several diagnostic modalities are used, with varying degrees of lack of sensitivity and specificity, and with a range of false negatives. A quarter of cases were treated solely on the basis of clinical, imaging, or histological suspicion, without confirmation of the diagnosis. Therefore, we report the case of a young Vietnamese woman who presented with a non-healing breast abscess and was diagnosed with breast tuberculosis based on the patient’s ethnicity, histological findings, lack of clinical response to conventional antibiotic therapy, and a good clinical response to antituberculosis treatment.