Nitric Oxide Controls the Immunopathology of Tuberculosis by Inhibiting NLRP3 Inflammasome-dependent Processing of IL-1β

Overview

Journal Nat Immunol

Date 2012 Nov 20

PMID 23160153

Citations 323

Authors

Bibhuti B Mishra

Vijay A K Rathinam

Gregory W Martens

Amanda J Martinot

Hardy Kornfeld

Katherine A Fitzgerald

Christopher M Sassetti

Affiliations

Soon will be listed here.

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.

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