Journal
IMMUNITY
Volume 42, Issue 4, Pages 744-755Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2015.03.004
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Funding
- Basic Science Research Program through the National Research Foundation of Korea - Ministry of Education, Science and Technology [2013R1A6A3A03024348]
- Crohn's and Colitis Foundation of America
- Michigan Gastrointestinal Peptide Research Center NIDDK [5P30DK034933]
- Wellcome Trust [098051, WT086418MA]
- National Institutes of Health [DK091191, DK095782]
- National Research Foundation of Korea [2013R1A6A3A03024348] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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.
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