Cutting edge: Caspase-1 independent IL-1β production is critical for host resistance to Mycobacterium tuberculosis and does not require TLR signaling in vivo

Katrin D. Mayer-Barber, Daniel L. Barber, Kevin Shenderov, Sandra D. White, Mark S. Wilson, Allen Cheever, David Kugler, Sara Hieny, Patricia Caspar, Gabriel Núñez, Dirk Schlueter, Richard A. Flavell, Fayyaz S. Sutterwala, Alan Sher

Research output: Contribution to journalArticle

Abstract

To investigate the respective contributions of TLR versus IL-1R mediated signals in MyD88 dependent control of Mycobacterium tuberculosis, we compared the outcome of M. tuberculosis infection in MyD88, TRIF/MyD88, IL-1R1, and IL-1β-deficient mice. All four strains displayed acute mortality with highly increased pulmonary bacterial burden suggesting a major role for IL-1β signaling in determining the MyD88 dependent phenotype. Unexpectedly, the infected MyD88 and TRIF/MyD88-deficient mice, rather than being defective in IL-1β expression, displayed increased cytokine levels relative to wild-type animals. Similarly, infected mice deficient in caspase-1 and ASC, which have critical functions in inflammasome-mediated IL-1β maturation, showed unimpaired IL-1β production and importantly, were considerably less susceptible to infection than IL-1β deficient mice. Together our findings reveal a major role for IL-1β in host resistance to M. tuberculosis and indicate that during this infection the cytokine can be generated by a mechanism that does not require TLR signaling or caspase-1.

Original languageEnglish (US)
Pages (from-to)3326-3330
Number of pages5
JournalJournal of Immunology
Volume184
Issue number7
DOIs
StatePublished - Apr 1 2010

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Mayer-Barber, K. D., Barber, D. L., Shenderov, K., White, S. D., Wilson, M. S., Cheever, A., Kugler, D., Hieny, S., Caspar, P., Núñez, G., Schlueter, D., Flavell, R. A., Sutterwala, F. S., & Sher, A. (2010). Cutting edge: Caspase-1 independent IL-1β production is critical for host resistance to Mycobacterium tuberculosis and does not require TLR signaling in vivo. Journal of Immunology, 184(7), 3326-3330. https://doi.org/10.4049/jimmunol.0904189