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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Clash of the Cytokine Titans: counter-regulation of interleukin-1 and type I interferon-mediated inflammatory responses.
Katrin D. Mayer-Barber,Bo Yan +1 more
TL;DR: How the type I interferon and interleukin-1 cytokine pathways represent distinct and specialized categories of inflammatory responses and how these key mediators of inflammation counter-regulate each other are discussed.
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HIF-1α Is an Essential Mediator of IFN-γ–Dependent Immunity to Mycobacterium tuberculosis
TL;DR: HIF-1α is identified as a novel regulator of IFN-γ–dependent immunity that coordinates an immunometabolic program essential for control of M. tuberculosis infection both in vitro and in vivo.
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NLRP3 inflammasome pathways in atherosclerosis.
TL;DR: The basic cellular and molecular mechanisms of NLRP3 inflammasome activation are introduced, and the current findings and therapeutic strategies that target NLR family Pyrin domain containing 3 inflammaome activation during the development and progression of atherosclerosis are discussed.
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Interferon Gamma Induces Reversible Metabolic Reprogramming of M1 Macrophages to Sustain Cell Viability and Pro-Inflammatory Activity
Feilong Wang,Song Zhang,Ryoung-Hoon Jeon,Ivan Vuckovic,Xintong Jiang,Amir Lerman,Clifford D.L. Folmes,Petras Dzeja,Joerg Herrmann +8 more
TL;DR: It is demonstrated that IFNγ induces a rapid activation of aerobic glycolysis followed by a reduction in oxidative phosphorylation in M1 macrophages, which sustains cell viability and inflammatory activity, while limiting reliance on mitochondrial oxidative metabolism.
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Post-translational regulation of inflammasomes
TL;DR: This review focuses on the emerging roles of post-translational modifications (PTMs) that regulate activation of the NLRP3, NLRP1, NLRC4, AIM2 and IFI16 inflammasomes.
References
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Erratum: NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals (Nature (2010) 464 (1357-1361))
Peter Duewell,Hajime Kono,Katey J. Rayner,Cherilyn M. Sirois,Gregory I. Vladimer,Franz Bauernfeind,George S. Abela,Luigi Franchi,Gabriel Núñez,Max Schnurr,Terje Espevik,Egil Lien,Katherine A. Fitzgerald,Kenneth L. Rock,Kathryn J. Moore,Samuel D. Wright,Veit Hornung,Eicke Latz +17 more
TL;DR: This corrects the article to show that the method used to derive the H2O2 “spatially aggregating force” is a two-step process, not a single step, like in the previous version of this paper.
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