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
Citations
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The Role of Interferons in Inflammation and Inflammasome Activation.
TL;DR: In the present review, recent findings regarding the cross talk of IFNs and inflammasomes are summarized and analyzed.
Journal ArticleDOI
Redox regulation of immunometabolism.
Jonathan Muri,Manfred Kopf +1 more
TL;DR: Mari et al. as discussed by the authors examined the crosstalk between metabolic and redox pathways and discussed their role in the proliferation, survival and function in T cells, B cells and macrophages.
Journal ArticleDOI
New Insights into Mechanisms Controlling the NLRP3 Inflammasome and Its Role in Lung Disease
TL;DR: The most recent contributions to the understanding of the regulatory mechanisms controlling activation of the NLRP3 inflammasome are reviewed and the contribution of theNLRP3inflammasomes to the pathology of lung diseases is discussed.
Journal ArticleDOI
Type I IFN Induces IL-10 Production in an IL-27–Independent Manner and Blocks Responsiveness to IFN-γ for Production of IL-12 and Bacterial Killing in Mycobacterium tuberculosis–Infected Macrophages
Finlay W. McNab,John Ewbank,Ashleigh Howes,Lúcia Moreira-Teixeira,Anna Martirosyan,Nico Ghilardi,Margarida Saraiva,Anne O'Garra +7 more
TL;DR: Investigation of the effect of type I IFN on M. tuberculosis–infected macrophages found that production of host-protective cytokines such as TNF-α, IL-12, and IL-1β is inhibited by exogenous type IIFN, whereas production of immunosuppressive IL-10 is promoted in an IL-27–independent manner.
Journal ArticleDOI
Toward targeting inflammasomes: insights into their regulation and activation.
TL;DR: The transcriptional regulation of inflammasome components and related proteins, the post-translational mechanisms of infammasome activation, and advances in the understanding of the structural basis of inflammatory diseases, neurodegeneration, and cancer are discussed.
References
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