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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Scaling of immune responses against intracellular bacterial infection
TL;DR: The effector responses triggered by activation of cytosolic PRRs, in particular the RIG‐I‐induced simultaneous rapid type I IFN induction and inflammasome activation, are crucial for timely control of bacterial infection by innate and adaptive immunity.
Journal ArticleDOI
IFN-γ extends the immune functions of Guanylate Binding Proteins to inflammasome-independent antibacterial activities during Francisella novicida infection.
Pierre Wallet,Sacha Benaoudia,Amandine Mosnier,Brice Lagrange,Amandine Martin,Helena Lindgren,Igor Golovliov,Fanny Michal,Pauline Basso,Sophia Djebali,Angelina Provost,Omran Allatif,Etienne Meunier,Petr Broz,Masahiro Yamamoto,Bénédicte F. Py,Eric Faudry,Anders Sjöstedt,Thomas Henry +18 more
TL;DR: Results indicate that GBPs are the master effectors of IFN-γ-mediated responses against F. novicida to control antibacterial immune responses in inflammasome-dependent and independent manners.
Journal ArticleDOI
Negative regulators and their mechanisms in NLRP3 inflammasome activation and signaling.
TL;DR: The identification and characterization of new players in the regulation of NLRP3 inflammasome may lead to the development of inflamasome‐targeting therapeutics against various inflammatory diseases related to NLRP2 inflammaome‐associated pathogenesis.
Journal ArticleDOI
MCL Plays an Anti-Inflammatory Role in Mycobacterium tuberculosis-Induced Immune Response by Inhibiting NF-κB and NLRP3 Inflammasome Activation.
Qingwen Zhang,Xinru Jiang,Weigang He,Kailin Wei,Jinxia Sun,Xiangyang Qin,Yuejuan Zheng,Xin Jiang +7 more
TL;DR: Micheliolide plays an important role in modulating Mtb-induced inflammatory response through PI3K/Akt/NF-κB pathway and subsequently downregulating the activation of NLRP3 inflammasome, therefore, MCL may represent as a potential drug candidate in the adjuvant treatment of TB by regulating host immune response.
Journal ArticleDOI
Copper Regulates the Canonical NLRP3 Inflammasome.
TL;DR: It is demonstrated that NLRP3 inflammasome activation is blocked by removing copper from the active site of superoxide dismutase 1, recapitulating impaired inflammaome function insuperoxide dismUTase 1–deficient mice, indicating that targeting the intracellular copper homeostasis has potential for the treatment ofNLRP3-dependent diseases.
References
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