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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Inflammation and tuberculosis: host‐directed therapies
Alimuddin Zumla,Martin Rao,Shreemanta Parida,Salmaan Keshavjee,Gail H. Cassell,Robert S. Wallis,R Axelsson-Robertsson,R Axelsson-Robertsson,M. Doherty,Jan Andersson,Markus Maeurer,Markus Maeurer +11 more
TL;DR: Current concepts of inflammation in TB disease are reviewed, candidate pathways for host‐directed therapies to achieve better clinical outcomes are discussed and biological agents or already approved drugs can be ‘re‐purposed’ to interfere with biologically relevant cellular checkpoints are discussed.
Journal ArticleDOI
Inflammasomes: Threat-Assessment Organelles of the Innate Immune System.
TL;DR: It is posited that upstream regulatory proteins, classically known as pattern-recognition receptors, operate to assess infectious and non-infectious threats to the host.
Journal ArticleDOI
Natural Compounds as Regulators of NLRP3 Inflammasome-Mediated IL-1β Production
József Tőzsér,Szilvia Benkő +1 more
TL;DR: This review aimed to provide an overview of studies that demonstrated the effect of plant-derived natural compounds on NLRP3 inflammasome-mediated IL-1β production and suggested that these compounds may be considered as complementary supplements in the treatment of chronic inflammatory diseases, consumed as preventive agents, and may also be consider as molecular tools to study NL RP3 function.
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Activation of NLRP3 inflammasomes contributes to hyperhomocysteinemia-aggravated inflammation and atherosclerosis in apoE-deficient mice
TL;DR: It is found that Hcy activated NLRP3 inflammasomes and promoted subsequent production of IL-1β and IL-18 in macrophages, which were blocked byNLRP3 gene silencing or Z-WEHD-FMK.
Journal ArticleDOI
Unsolved Mysteries in NLR Biology.
TL;DR: The various mechanisms of sensing and activation proposed for NLRP3 and other inflammasome activators are reviewed and the role of NLRC3,NLRP6, NLRP12, and NLRX1 as inhibitors are discussed and how they are activated and function in their roles to limit inflammation.
References
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Erratum: NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals (Nature (2010) 464 (1357-1361))
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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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