IL-1β promotes antimicrobial immunity in macrophages by regulating TNFR signaling and caspase-3 activation

Pushpa Jayaraman, Isabel Sada-Ovalle, Tomoyasu Nishimura, Ana C. Anderson, Vijay K. Kuchroo, Heinz G. Remold, Samuel M. Behar

Research output: Contribution to journalArticle

115 Citations (Scopus)

Abstract

In vivo control of Mycobacterium tuberculosis reflects the balance between host immunity and bacterial evasion strategies. Effector Th1 cells that mediate protective immunity by depriving the bacterium of its intracellular niche are regulated to prevent overexuberant inflammation. One key immunoregulatory molecule is Tim3. Although Tim3 is generally recognized to down-regulate Th1 responses, we recently described that its interaction with Galectin-9 expressed by M. tuberculosis-infected macrophages stimulates IL-1β secretion, which is essential for survival in the mouse model. Why IL-1β is required for host resistance to M. tuberculosis infection is unknown. In this article, we show that IL-1β directly kills M. tuberculosis in murine and human macrophages and does so through the recruitment of other antimicrobial effector molecules. IL-1β directly augments TNF signaling in macrophages through the upregulation of TNF secretion and TNFR1 cell surface expression, and results in activation of caspase-3. Thus, IL-1β and downstream TNF production lead to caspase-dependent restriction of intracellular M. tuberculosis growth.

Original languageEnglish
Pages (from-to)4196-4204
Number of pages9
JournalJournal of Immunology
Volume190
Issue number8
DOIs
Publication statusPublished - 2013 Apr 15
Externally publishedYes

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Interleukin-1
Mycobacterium tuberculosis
Caspase 3
Immunity
Macrophages
Receptors, Tumor Necrosis Factor, Type I
Galectins
Th1 Cells
Mycobacterium Infections
Caspases
Up-Regulation
Down-Regulation
Inflammation
Bacteria
Survival
Growth

ASJC Scopus subject areas

  • Immunology

Cite this

Jayaraman, P., Sada-Ovalle, I., Nishimura, T., Anderson, A. C., Kuchroo, V. K., Remold, H. G., & Behar, S. M. (2013). IL-1β promotes antimicrobial immunity in macrophages by regulating TNFR signaling and caspase-3 activation. Journal of Immunology, 190(8), 4196-4204. https://doi.org/10.4049/jimmunol.1202688

IL-1β promotes antimicrobial immunity in macrophages by regulating TNFR signaling and caspase-3 activation. / Jayaraman, Pushpa; Sada-Ovalle, Isabel; Nishimura, Tomoyasu; Anderson, Ana C.; Kuchroo, Vijay K.; Remold, Heinz G.; Behar, Samuel M.

In: Journal of Immunology, Vol. 190, No. 8, 15.04.2013, p. 4196-4204.

Research output: Contribution to journalArticle

Jayaraman, P, Sada-Ovalle, I, Nishimura, T, Anderson, AC, Kuchroo, VK, Remold, HG & Behar, SM 2013, 'IL-1β promotes antimicrobial immunity in macrophages by regulating TNFR signaling and caspase-3 activation', Journal of Immunology, vol. 190, no. 8, pp. 4196-4204. https://doi.org/10.4049/jimmunol.1202688
Jayaraman, Pushpa ; Sada-Ovalle, Isabel ; Nishimura, Tomoyasu ; Anderson, Ana C. ; Kuchroo, Vijay K. ; Remold, Heinz G. ; Behar, Samuel M. / IL-1β promotes antimicrobial immunity in macrophages by regulating TNFR signaling and caspase-3 activation. In: Journal of Immunology. 2013 ; Vol. 190, No. 8. pp. 4196-4204.
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