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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Mycobacterium tuberculosis Evasion of Guanylate Binding Protein-Mediated Host Defense in Mice Requires the ESX1 Secretion System
TL;DR: In this article , the authors examined the importance of a cluster of five Guanylate binding proteins (GBPs) on mouse chromosome 3 in controlling Mycobacterial infection and found that GBPs on chromosome 3 do not contribute to the control of Mtb replication or the associated host response to infection.
Journal ArticleDOI
Regulação do inflamassoma NLRP3: bioquímica e além dela
TL;DR: In this paper, a plataforma molecular denominada inflamasoma is defined, and a set of mecanismos mas importantes en la modulación de la actividad del inflamasmoma are presented.
Book ChapterDOI
Type I Interferon and Interleukin-1 Driven Inflammatory Pathways as Targets for HDT in Tuberculosis
TL;DR: This article reviewed the current understanding of IL-1 and type I IFNs in TB pathogenesis and expand on more recent findings that point to the IL1 and Type I IFN pathways as promising targets for HDT.
Book ChapterDOI
Metabolic Host Response to Intracellular Infections.
TL;DR: An overview of the crucial role of fundamental metabolic host responses in the generation of protective immunity to intracellular bacterial pathogens is provided and some of the mechanisms used by these pathogens to exploit the host metabolic response to their own advantage are discussed.
References
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Journal ArticleDOI
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Journal ArticleDOI
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.
Journal ArticleDOI
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