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- Title
Nitric oxide controls the immunopathology of tuberculosis by inhibiting NLRP3 inflammasome-dependent processing of IL-1?
- Authors
Mishra, Bibhuti B; Rathinam, Vijay A K; Martens, Gregory W; Martinot, Amanda J; Kornfeld, Hardy; Fitzgerald, Katherine A; Sassetti, Christopher M
- 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-? (IFN-?). 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.
- Subjects
NITRIC oxide; IMMUNOPATHOLOGY; TUBERCULOSIS; INTERLEUKIN-1; NLRP3 protein; CASPASES; NATURAL immunity; INFLAMMATION
- Publication
Nature Immunology, 2012, Vol 14, Issue 1, p52
- ISSN
1529-2908
- Publication type
Article
- DOI
10.1038/ni.2474