Cited by 571Inflammasome and immune disordersTuberculosis Research and EpidemiologyImmune Response and Inflammation

Nitric oxide controls the immunopathology of tuberculosis by inhibiting NLRP3 inflammasome–dependent processing of IL-1β

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Mishra, Bibhuti B, Rathinam, Vijay A K, Martens, Gregory W, Martinot, Amanda J, Kornfeld, Hardy, Fitzgerald, Katherine A, Sassetti, Christopher M·2013·Nature Immunology

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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  • NO directly blocks inflammasome activation via nitrosylation of NLRP3, thereby preventing excessive tissue damage during M. tuberculosis infection.

    “Similarly, NO directly blocks inflammasome activation via nitrosylation of NLRP3, thereby preventing excessive tissue damage in the course of M. tuberculosis infection (102, 103).”

    From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [103]

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Research works printed but not linked: 1

  1. [45]Nandi B Behar SM Regulation of neutrophils by interferon-gamma limits lung inflammation during tuberculosis infection J. Exp. Med 2011 208 2251 2262 21967766 PMC3201199

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Authors
Mishra, B. B., Rathinam, V. A. K., Martens, G. W., Martinot, A. J., Kornfeld, H., Fitzgerald, K. A., & Sassetti, C. M.
Affiliations
  • University of Massachusetts Chan Medical School (US)
  • Harvard University (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
Sassetti, Christopher M
Venue
Nature Immunology
Published
2012-11-18
Volume
14
Issue
1
Pages
52-60
ISSN
  • 1529-2908 (ISSN-L)
  • 1529-2916
OpenAlex
W2048884877
Cited by
571
References
49
Citations by year
2026: 24 · 2025: 27 · 2024: 29 · 2023: 39 · 2022: 47 · 2021: 53 · 2020: 46 · 2019: 43 · 2018: 51 · 2017: 46 · 2016: 46 · 2015: 40 · 2014: 40 · 2013: 37 · 2012: 3
FWCI
15.44
Type
journal article
Language
en
Open access
Locations
  • Nature Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Heart, Lung, and Blood Institute (R01HL064884, R01HL081149, HL064884)
  • National Institute of Allergy and Infectious Diseases (AI064282, R01AI064282, AI083713, U54AI057159, R01AI083713, T32AI007638)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
  • Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords
nitric oxide, NLRP3 inflammasome, interleukin-1β processing, tuberculosis, immunopathology, Mycobacterium tuberculosis, nitrosylation, interferon-gamma, innate immunity, chronic infection, adaptive immunity
MeSH terms
NLR Family, Pyrin Domain-Containing 3 Protein, Animals, Carrier Proteins, Cells, Cultured, Humans, Immunity, Innate, Interferon-gamma, Mice, Inbred C57BL, Mycobacterium tuberculosis, Nitric Oxide, Tuberculosis, Signal Transduction, Mice, Knockout, Protein Modification, Translational, Mice, Interleukin-1beta, Protein Multimerization, Inflammasomes

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