Nitric oxide controls the immunopathology of tuberculosis by inhibiting NLRP3 inflammasome-dependent processing of IL-1β.
Bibhuti B. Mishra,Vijay A. K. Rathinam,Gregory W. Martens,Amanda J. Martinot,Hardy Kornfeld,Katherine A. Fitzgerald,Christopher M. Sassetti,Christopher M. Sassetti +7 more
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TLDR
By exogenously controlling the replication of Mycobacterium tuberculosis in vivo, the requirement for antimicrobial immunity is obviated and it is discovered that both IL-1 production and infection-induced immunopathology were suppressed by lymphocyte-derived interferon-γ (IFN-γ).Abstract:
Interleukin 1 (IL-1) is an important mediator of innate immunity but can also promote inflammatory tissue damage. During chronic infections such as tuberculosis, the beneficial antimicrobial role of IL-1 must be balanced with the need to prevent immunopathology. By exogenously controlling the replication of Mycobacterium tuberculosis in vivo, we obviated the requirement for antimicrobial immunity and discovered that both IL-1 production and infection-induced immunopathology were suppressed by lymphocyte-derived interferon-γ (IFN-γ). This effect was mediated by nitric oxide (NO), which we found specifically inhibited assembly of the NLRP3 inflammasome via thiol nitrosylation. Our data indicate that the NO produced as a result of adaptive immunity is indispensable in modulating the destructive innate inflammatory responses elicited during persistent infections.read more
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Impaired Pulmonary Nitric Oxide Bioavailability in Pulmonary Tuberculosis: Association With Disease Severity and Delayed Mycobacterial Clearance With Treatment
Anna P. Ralph,Tsin W. Yeo,Cheryl M. Salome,Govert Waramori,Gysje J. Pontororing,Enny Kenangalem,Sandjaja,Emiliana Tjitra,Richard Lumb,Graeme P. Maguire,Ric N. Price,Mark D. Chatfield,Paul Kelly,Nicholas M. Anstey +13 more
TL;DR: Investigating relationships between fractional exhale NO (FENO) and initial pulmonary tuberculosis severity, change during treatment, and relationship with conversion of sputum culture to negative at 2 months found impaired pulmonary NO bioavailability is associated with more-severe disease and delayed mycobacterial clearance.
Journal ArticleDOI
Sex differences in the C57BL/6 model of Mycobacterium tuberculosis infection.
TL;DR: It is revealed that disease progression upon aerosol infection with Mycobacterium tuberculosis (Mtb) was accelerated in males resulting in increased morbidity and mortality compared to females, and the urgent need to include and separately analyze both sexes in future animal studies of Tb is emphasized.
Journal ArticleDOI
Macrophage-Microglia Networks Drive M1 Microglia Polarization After Mycobacterium Infection
Yongwei Qin,Xiaolei Sun,Xiaoyi Shao,Chun Cheng,Jinrong Feng,Wei Sun,Delin Gu,Wei Liu,Feifan Xu,Yinong Duan +9 more
TL;DR: It is found that BV2 treated with conditioned media from cultures of macrophages infected with Mycobacterium marinum induced the expression of M1 phenotypic genes but reduced that of M2 phenotypesic genes such as Arginase 1, Ym1, and CD163, which suggest that polarization of microglia is partly mediated through macrophage-microglia interactions as a priming signal.
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Caspases as the key effectors of inflammatory responses against bacterial infection.
Ryosuke Uchiyama,Hiroko Tsutsui +1 more
TL;DR: The functional roles and activation mechanisms of caspase-1/-11 in innate immune responses against bacterial infection and Fas-mediated casp enzyme-8 activation and inflammatory cytokine production have been shown to play a significant role in the regulation of bacterial infections.
Journal ArticleDOI
A Genetic Screen Reveals that Synthesis of 1,4-Dihydroxy-2-Naphthoate (DHNA), but Not Full-Length Menaquinone, Is Required for Listeria monocytogenes Cytosolic Survival
Grischa Y. Chen,Courtney E. McDougal,Marc A. D’Antonio,Jonathan L. Portman,John-Demian Sauer +4 more
TL;DR: A novel genetic screen identified determinants of L. monocytogenes cytosolic survival and virulence and identified a role for the synthesis of the menaquinone precursor 1,4-dihydroxy-2-naphthoate (DHNA) in cytosol survival.
References
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