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

Sang Uk Seo, Nobuhiko Kamada, Raúl Muñoz-Planillo, Yungi Kim, Donghyun Kim, Yukiko Koizumi, Mizuho Hasegawa, Stephanie D. Himpsl, Hilary P. Browne, Trevor D. Lawley, Harry L T Mobley, Naohiro Inohara, Gabriel Núñez

Research output: Contribution to journalArticle

106 Citations (Scopus)

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 languageEnglish
Pages (from-to)744-755
Number of pages12
JournalImmunity
Volume42
Issue number4
DOIs
Publication statusPublished - 2015 Apr 21
Externally publishedYes

Fingerprint

Inflammasomes
Interleukin-1
Microbiota
Monocytes
Inflammation
Wounds and Injuries
Intestines
Mirabilis
Proteus mirabilis
Hemolysin Proteins
Interleukin-1 Receptors
Chemokine Receptors
Enterobacteriaceae
Salmonella

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 journalArticle

Seo, SU, Kamada, N, Muñoz-Planillo, R, Kim, Y, Kim, D, Koizumi, Y, Hasegawa, M, Himpsl, SD, Browne, HP, Lawley, TD, Mobley, HLT, Inohara, N & Núñez, G 2015, 'Distinct Commensals Induce Interleukin-1β via NLRP3 Inflammasome in Inflammatory Monocytes to Promote Intestinal Inflammation in Response to Injury', Immunity, vol. 42, no. 4, pp. 744-755. https://doi.org/10.1016/j.immuni.2015.03.004
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. / Distinct Commensals Induce Interleukin-1β via NLRP3 Inflammasome in Inflammatory Monocytes to Promote Intestinal Inflammation in Response to Injury. In: Immunity. 2015 ; Vol. 42, No. 4. pp. 744-755.
@article{9def039af79344118d91e705f7240655,
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 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.",
author = "Seo, {Sang Uk} and Nobuhiko Kamada and Ra{\'u}l Mu{\~n}oz-Planillo and Yungi Kim and Donghyun Kim and Yukiko Koizumi and Mizuho Hasegawa and Himpsl, {Stephanie D.} and Browne, {Hilary P.} and Lawley, {Trevor D.} and Mobley, {Harry L T} and Naohiro Inohara and Gabriel N{\'u}{\~n}ez",
year = "2015",
month = "4",
day = "21",
doi = "10.1016/j.immuni.2015.03.004",
language = "English",
volume = "42",
pages = "744--755",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "4",

}

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.

UR - http://www.scopus.com/inward/record.url?scp=84928175356&partnerID=8YFLogxK

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

VL - 42

SP - 744

EP - 755

JO - Immunity

JF - Immunity

SN - 1074-7613

IS - 4

ER -