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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Inflammasome activation and regulation: toward a better understanding of complex mechanisms.
TL;DR: The most recent advances and remaining challenges in understanding the ordered inflammasome assembly and activation upon sensing of diverse stimuli, as well as the tight regulations of these processes are summarized.
Journal ArticleDOI
Microenvironments in tuberculous granulomas are delineated by distinct populations of macrophage subsets and expression of nitric oxide synthase and arginase isoforms
Joshua T. Mattila,Olabisi Ojo,Diane Kepka-Lenhart,Simeone Marino,Jin Hee Kim,Seok Yong Eum,Laura E. Via,Clifton E. Barry,Edwin Klein,Denise E. Kirschner,Sidney M. Morris,Philana Ling Lin,JoAnne L. Flynn +12 more
TL;DR: The combination of phenotypic and functional markers support that granulomas have organized microenvironments that balance antimicrobial anti-inflammatory responses to limit pathology in the lungs.
Journal ArticleDOI
In search of a new paradigm for protective immunity to TB
Cláudio Nunes-Alves,Matthew G. Booty,Stephen M. Carpenter,Pushpa Jayaraman,Alissa C. Rothchild,Samuel M. Behar +5 more
TL;DR: Recent advances in the understanding of the immune control of M. tuberculosis are discussed and how this knowledge could be used for vaccine design and evaluation is discussed.
Journal ArticleDOI
CD4 T Cell-Derived IFN-γ Plays a Minimal Role in Control of Pulmonary Mycobacterium tuberculosis Infection and Must Be Actively Repressed by PD-1 to Prevent Lethal Disease.
Shunsuke Sakai,Keith D. Kauffman,Michelle A. Sallin,Arlene H. Sharpe,Howard A. Young,Vitaly V. Ganusov,Daniel L. Barber +6 more
TL;DR: The primary role for T cell-derived IFN-γ in Mtb infection is at extra-pulmonary sites, and the host-protective subset of CD4 T cells requires negative regulation of IFN–γ production by PD-1 to prevent lethal immune-mediated pathology.
Journal ArticleDOI
The regulation of inflammation by interferons and their STATs
TL;DR: The goal of this review is to give an overview of the different facets of the inflammatory process that show regulatory input by IFN/STAT.
References
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