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

作者：Seo Sang Uk; Kamada Nobuhiko; Munoz Planillo Raul; Kim Yun Gi; Kim Donghyun; Koizumi Yukiko; Hasegawa Mizuho; Himpsl Stephanie D; Browne Hilary P; Lawley Trevor D; Mobley Harry L T; Inohara Naohiro; Nunez Gabriel^*

来源：Immunity, 2015, 42(4): 744-755.

DOI：10.1016/j.immuni.2015.03.004

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-1 beta (IL-1 beta) release upon intestinal injury and that this is mediated via the NLRP3 inflammasome. Enterobacteriaceae and in particular the pathobiont Proteus mirabilis, induced robust IL-1 beta release that was comparable to that induced by the pathogen Salmonella. Upon epithelial injury, production of IL-1 beta in the intestine was largely mediated by intestinal Ly6C(high) monocytes, required chemokine receptor CCR2 and was abolished by deletion of IL-1 beta 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 in vivo. Thus, upon intestinal injury, selective members of the microbiota stimulate newly recruited monocytes to induce NLRP3-dependent IL-1 beta release, which promotes inflammation in the intestine.

• 出版日期2015-4-21