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

研究成果: Article

119 引用 (Scopus)

抜粋

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.

元の言語English
ページ(範囲)744-755
ページ数12
ジャーナルImmunity
42
発行部数4
DOI
出版物ステータスPublished - 2015 4 21
外部発表Yes

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

これを引用

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