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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Activation and regulation of the inflammasomes
TL;DR: The complex regulatory mechanisms that facilitate a balanced but effective inflammasome-mediated immune response are discussed, and the similarities to another molecular signalling platform — the apoptosome — that monitors cellular health are highlighted.
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Petr Broz,Vishva M. Dixit +1 more
TL;DR: This Review discusses the recent developments in inflammasome research with a focus on the molecular mechanisms that govern inflammaome assembly, signalling and regulation.
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The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation.
TL;DR: Current understanding of the mechanisms ofNLRP3 inflammasome activation by multiple signaling events, and its regulation by post-translational modifications and interacting partners of NLRP3 are summarized.
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Regulation of inflammasome activation
TL;DR: Genetic studies indicate that mutations in NLRP1, NLRP3, NLRC4, and AIM2 are linked with the development of auto‐inflammatory diseases, enterocolitis, and cancer and transform the understanding of the basic biology and clinical relevance of inflammasomes.
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Dopamine Controls Systemic Inflammation through Inhibition of NLRP3 Inflammasome
TL;DR: DA and DRD1 signaling prevent NLRP3 inflammasome-dependent inflammation, including neurotoxin-induced neuroinflammation, LPS-induced systemic inflammation, and monosodium urate crystal (MSU)-induced peritoneal inflammation.
References
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Tuberculosis Susceptibility of Diabetic Mice
Gregory W. Martens,Meltem Cevik Arikan,Jinhee Lee,Fucheng Ren,Dale L. Greiner,Hardy Kornfeld +5 more
TL;DR: It is shown that Mtb infection of STZ-treated mice provides a useful model to study the effects of hyperglycemia on immunity, and indicates that the initiation of adaptive immunity is impaired by chronic hyper glycemia, resulting in a higher steady-state burden of Mtb in the lung.
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Granuloma formation and host defense in chronic Mycobacterium tuberculosis infection requires PYCARD/ASC but not NLRP3 or caspase-1.
Erin McElvania TeKippe,Irving C. Allen,Paul D. Hulseberg,Jonathan Tabb Sullivan,Jessica R. McCann,Matyas Sandor,Miriam Braunstein,Jenny P.-Y. Ting +7 more
TL;DR: It is demonstrated that PYCARD exerts a novel inflammasome-independent role during chronic Mtb infection by containing the bacteria in granulomas, as shown by an abrupt decrease in survival of Pycard−/− mice.
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Fredric Carlsson,Janice Kim,Calin Dan Dumitru,Kai H. Barck,Richard A.D. Carano,Mei Sun,Lauri Diehl,Eric J. Brown +7 more
TL;DR: Infection of wild type and ASC-deficient mice demonstrated that Esx-1-dependent inflammasome activation exacerbated disease without restricting bacterial growth, indicating a host-detrimental role of this inflammatory pathway in mycobacterial infection.
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Immortalization of cloned mouse splenic macrophages with a retrovirus containing the v-raf/mil and v-myc oncogenes
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