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NLRC4-driven interleukin-1β production discriminates between pathogenic and commensal bacteria and promotes host intestinal defense

Intestinal phagocytes transport oral antigens and promote immune tolerance, but their role in innate immune responses remains unclear. Here we report that intestinal phagocytes are anergic to Toll-like receptor ligands or commensals, but constitutively express pro-interleukin-1β (proIL-1β). Upon inf...

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Autores principales: Franchi, Luigi, Kamada, Nobuhiko, Nakamura, Yuumi, Burberry, Aaron, Kuffa, Peter, Suzuki, Shiho, Shaw, Michael H., Kim, Yun-Gi, Núñez, Gabriel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3361590/
https://www.ncbi.nlm.nih.gov/pubmed/22484733
http://dx.doi.org/10.1038/ni.2263
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author Franchi, Luigi
Kamada, Nobuhiko
Nakamura, Yuumi
Burberry, Aaron
Kuffa, Peter
Suzuki, Shiho
Shaw, Michael H.
Kim, Yun-Gi
Núñez, Gabriel
author_facet Franchi, Luigi
Kamada, Nobuhiko
Nakamura, Yuumi
Burberry, Aaron
Kuffa, Peter
Suzuki, Shiho
Shaw, Michael H.
Kim, Yun-Gi
Núñez, Gabriel
author_sort Franchi, Luigi
collection PubMed
description Intestinal phagocytes transport oral antigens and promote immune tolerance, but their role in innate immune responses remains unclear. Here we report that intestinal phagocytes are anergic to Toll-like receptor ligands or commensals, but constitutively express pro-interleukin-1β (proIL-1β). Upon infection with pathogenic Salmonella or Pseudomonas, intestinal phagocytes produce mature IL-1β through the NLRC4 inflammasome, but not tumor necrosis factor or IL-6. Mice deficient in NLRC4 or IL-1 receptor on a Balb/c background were highly susceptible to orogastric but not intraperitoneal infection with Salmonella. Increased lethality was preceded by impaired expression of endothelial adhesion molecules, lower neutrophil recruitment, and poor intestinal pathogen clearance. Thus, NLRC4-dependent IL-1β production by intestinal phagocytes represents a specific response discriminating pathogenic from commensal bacteria and contributes to host defense in the intestine.
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spelling pubmed-33615902012-11-01 NLRC4-driven interleukin-1β production discriminates between pathogenic and commensal bacteria and promotes host intestinal defense Franchi, Luigi Kamada, Nobuhiko Nakamura, Yuumi Burberry, Aaron Kuffa, Peter Suzuki, Shiho Shaw, Michael H. Kim, Yun-Gi Núñez, Gabriel Nat Immunol Article Intestinal phagocytes transport oral antigens and promote immune tolerance, but their role in innate immune responses remains unclear. Here we report that intestinal phagocytes are anergic to Toll-like receptor ligands or commensals, but constitutively express pro-interleukin-1β (proIL-1β). Upon infection with pathogenic Salmonella or Pseudomonas, intestinal phagocytes produce mature IL-1β through the NLRC4 inflammasome, but not tumor necrosis factor or IL-6. Mice deficient in NLRC4 or IL-1 receptor on a Balb/c background were highly susceptible to orogastric but not intraperitoneal infection with Salmonella. Increased lethality was preceded by impaired expression of endothelial adhesion molecules, lower neutrophil recruitment, and poor intestinal pathogen clearance. Thus, NLRC4-dependent IL-1β production by intestinal phagocytes represents a specific response discriminating pathogenic from commensal bacteria and contributes to host defense in the intestine. 2012-05 /pmc/articles/PMC3361590/ /pubmed/22484733 http://dx.doi.org/10.1038/ni.2263 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Franchi, Luigi
Kamada, Nobuhiko
Nakamura, Yuumi
Burberry, Aaron
Kuffa, Peter
Suzuki, Shiho
Shaw, Michael H.
Kim, Yun-Gi
Núñez, Gabriel
NLRC4-driven interleukin-1β production discriminates between pathogenic and commensal bacteria and promotes host intestinal defense
title NLRC4-driven interleukin-1β production discriminates between pathogenic and commensal bacteria and promotes host intestinal defense
title_full NLRC4-driven interleukin-1β production discriminates between pathogenic and commensal bacteria and promotes host intestinal defense
title_fullStr NLRC4-driven interleukin-1β production discriminates between pathogenic and commensal bacteria and promotes host intestinal defense
title_full_unstemmed NLRC4-driven interleukin-1β production discriminates between pathogenic and commensal bacteria and promotes host intestinal defense
title_short NLRC4-driven interleukin-1β production discriminates between pathogenic and commensal bacteria and promotes host intestinal defense
title_sort nlrc4-driven interleukin-1β production discriminates between pathogenic and commensal bacteria and promotes host intestinal defense
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3361590/
https://www.ncbi.nlm.nih.gov/pubmed/22484733
http://dx.doi.org/10.1038/ni.2263
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