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 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.
| Original language | English |
|---|---|
| Pages (from-to) | 744-755 |
| Number of pages | 12 |
| Journal | Immunity |
| Volume | 42 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2015 Apr 21 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Immunology and Allergy
- Infectious Diseases
- Immunology
- Medicine(all)
Cite this
Distinct Commensals Induce Interleukin-1β via NLRP3 Inflammasome in Inflammatory Monocytes to Promote Intestinal Inflammation in Response to Injury. / Seo, Sang Uk; Kamada, Nobuhiko; Muñoz-Planillo, Raúl; Kim, Yungi; Kim, Donghyun; Koizumi, Yukiko; Hasegawa, Mizuho; Himpsl, Stephanie D.; Browne, Hilary P.; Lawley, Trevor D.; Mobley, Harry L T; Inohara, Naohiro; Núñez, Gabriel.
In: Immunity, Vol. 42, No. 4, 21.04.2015, p. 744-755.Research output: Contribution to journal › Article
}
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, Yungi
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
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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UR - http://www.scopus.com/inward/citedby.url?scp=84928175356&partnerID=8YFLogxK
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 -