title: Distinct Commensals Induce Interleukin-1β via NLRP3 Inflammasome in Inflammatory Monocytes to Promote Intestinal Inflammation in Response to Injury.
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 via the NLRP3 inflammasome. Enterobacteriaceae and in 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 Ly6C(high) 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 in vivo. 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.
authors: Department of Pathology and Comprehensive Cancer Center, The University of Michigan Medical School, 1500 East Medical Center Drive, Ann Arbor, MI 48109, USA.
authors: Sang-Uk
authors: SU
authors: Seo
authors: Division of Gastroenterology, Department of Internal Medicine, The University of Michigan Medical School, 1500 East Medical Center Drive, Ann Arbor, MI 48109, USA.
authors: Nobuhiko
authors: N
authors: Kamada
authors: Department of Pathology and Comprehensive Cancer Center, The University of Michigan Medical School, 1500 East Medical Center Drive, Ann Arbor, MI 48109, USA.
authors: Raúl
authors: R
authors: Muñoz-Planillo
authors: Department of Pathology and Comprehensive Cancer Center, The University of Michigan Medical School, 1500 East Medical Center Drive, Ann Arbor, MI 48109, USA.
authors: Yun-Gi
authors: YG
authors: Kim
authors: Department of Pathology and Comprehensive Cancer Center, The University of Michigan Medical School, 1500 East Medical Center Drive, Ann Arbor, MI 48109, USA.
authors: Donghyun
authors: D
authors: Kim
authors: Department of Pathology and Comprehensive Cancer Center, The University of Michigan Medical School, 1500 East Medical Center Drive, Ann Arbor, MI 48109, USA.
authors: Yukiko
authors: Y
authors: Koizumi
authors: Department of Pathology and Comprehensive Cancer Center, The University of Michigan Medical School, 1500 East Medical Center Drive, Ann Arbor, MI 48109, USA.
authors: Mizuho
authors: M
authors: Hasegawa
authors: Department of Microbiology and Immunology, The University of Michigan Medical School, 1500 East Medical Center Drive, Ann Arbor, MI 48109, USA.
authors: Stephanie D
authors: SD
authors: Himpsl
authors: Bacterial Pathogenesis Laboratory, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
authors: Hilary P
authors: HP
authors: Browne
authors: Bacterial Pathogenesis Laboratory, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
authors: Trevor D
authors: TD
authors: Lawley
authors: Department of Microbiology and Immunology, The University of Michigan Medical School, 1500 East Medical Center Drive, Ann Arbor, MI 48109, USA.
authors: Harry L T
authors: HL
authors: Mobley
authors: Department of Pathology and Comprehensive Cancer Center, The University of Michigan Medical School, 1500 East Medical Center Drive, Ann Arbor, MI 48109, USA.
authors: Naohiro
authors: N
authors: Inohara
authors: Department of Pathology and Comprehensive Cancer Center, The University of Michigan Medical School, 1500 East Medical Center Drive, Ann Arbor, MI 48109, USA. Electronic address: gabriel.nunez@umich.edu.
authors: Gabriel
authors: G
authors: Núñez
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation; D006460:Hemolysin Proteins / Q000235:genetics / Q000276:immunology; D058847:Inflammasomes / Q000235:genetics / Q000276:immunology*; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology*; D007422:Intestines / Q000276:immunology / Q000293:injuries / Q000382:microbiology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D064307:Microbiota / Q000276:immunology*; D009000:Monocytes / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D011512:Proteus Infections / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D011513:Proteus mirabilis / Q000276:immunology; D054390:Receptors, CCR2 / Q000235:genetics / Q000276:immunology; D012475:Salmonella / Q000276:immunology; D012480:Salmonella Infections / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D015398:Signal Transduction; D013559:Symbiosis / Q000276:immunology*
chemical_list: D000950:Antigens, Ly; D002352:Carrier Proteins; C515335:Ccr2 protein, mouse; D006460:Hemolysin Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; C494192:Ly-6C antigen, mouse; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D054390:Receptors, CCR2