TY - JOUR
T1 - Distinct Commensals Induce Interleukin-1β via NLRP3 Inflammasome in Inflammatory Monocytes to Promote Intestinal Inflammation in Response to Injury
AU - Seo, Sang Uk
AU - Kamada, Nobuhiko
AU - Muñoz-Planillo, Raúl
AU - Kim, Yun Gi
AU - Kim, Donghyun
AU - Koizumi, Yukiko
AU - Hasegawa, Mizuho
AU - Himpsl, Stephanie D.
AU - Browne, Hilary P.
AU - Lawley, Trevor D.
AU - Mobley, Harry L.T.
AU - Inohara, Naohiro
AU - Núñez, Gabriel
N1 - Funding Information:
We thank Grace Chen for critical review of the manuscript and Eric Pamer for proving mutant mice. We thank the University of Michigan Host Microbiome Initiative for support. This work is supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology 2013R1A6A3A03024348 (S.-U.S.), a Career Development award from the Crohn’s and Colitis Foundation of America (N.K.), the Michigan Gastrointestinal Peptide Research Center NIDDK 5P30DK034933 (N.K.), grants 098051 and WT086418MA from the Wellcome Trust (T.D.L.) and DK091191 and DK095782 from the National Institutes of Health (G.N.).
Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/4/21
Y1 - 2015/4/21
N2 - 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.
AB - 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.
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U2 - 10.1016/j.immuni.2015.03.004
DO - 10.1016/j.immuni.2015.03.004
M3 - Article
C2 - 25862092
AN - SCOPUS:84928175356
VL - 42
SP - 744
EP - 755
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 4
ER -