Distinct Commensals Induce Interleukin-1β via NLRP3 Inflammasome in Inflammatory Monocytes to Promote Intestinal Inflammation in Response to Injury

Sang Uk Seo, Nobuhiko Kamada, Raúl Muñoz-Planillo, Yun Gi Kim, Donghyun Kim, Yukiko Koizumi, Mizuho Hasegawa, Stephanie D. Himpsl, Hilary P. Browne, Trevor D. Lawley, Harry L.T. Mobley, Naohiro Inohara, Gabriel Núñez

Research output: Contribution to journalArticle

127 Citations (Scopus)

Abstract

The microbiota stimulates inflammation, but the signaling pathways and the members of the microbiota involved remain poorly understood. We found that the microbiota induces interleukin-1β (IL-1β) release upon intestinal injury and that this is mediated viatheNLRP3 inflammasome. Enterobacteriaceae andin particular the pathobiont Proteus mirabilis, induced robust IL-1β release that was comparable to that induced by the pathogen Salmonella. Upon epithelial injury, production of IL-1β in the intestine was largely mediated by intestinal Ly6Chigh monocytes, required chemokine receptor CCR2 and was abolished by deletion of IL-1β in CCR2+ blood monocytes. Furthermore, colonization with P.mirabilis promoted intestinal inflammation upon intestinal injury via the production of hemolysin, which required NLRP3 and IL-1 receptor signaling invivo. Thus, upon intestinal injury, selective members of the microbiota stimulate newly recruited monocytes to induce NLRP3-dependent IL-1β release, which promotes inflammation in the intestine.

Original languageEnglish
Pages (from-to)744-755
Number of pages12
JournalImmunity
Volume42
Issue number4
DOIs
Publication statusPublished - 2015 Apr 21
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Seo, S. U., Kamada, N., Muñoz-Planillo, R., Kim, Y. G., Kim, D., Koizumi, Y., Hasegawa, M., Himpsl, S. D., Browne, H. P., Lawley, T. D., Mobley, H. L. T., Inohara, N., & Núñez, G. (2015). Distinct Commensals Induce Interleukin-1β via NLRP3 Inflammasome in Inflammatory Monocytes to Promote Intestinal Inflammation in Response to Injury. Immunity, 42(4), 744-755. https://doi.org/10.1016/j.immuni.2015.03.004