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Eosinophils suppress Th1 responses and restrict bacterially induced gastrointestinal inflammation

Eosinophils are predominantly known for their contribution to allergy. Here, we have examined the function and regulation of gastrointestinal eosinophils in the steady-state and during infection with Helicobacter pylori or Citrobacter rodentium. We find that eosinophils are recruited to sites of inf...

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Autores principales: Arnold, Isabelle C., Artola-Borán, Mariela, Tallón de Lara, Paulino, Kyburz, Andreas, Taube, Christian, Ottemann, Karen, van den Broek, Maries, Yousefi, Shida, Simon, Hans-Uwe, Müller, Anne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6080907/
https://www.ncbi.nlm.nih.gov/pubmed/29970473
http://dx.doi.org/10.1084/jem.20172049
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author Arnold, Isabelle C.
Artola-Borán, Mariela
Tallón de Lara, Paulino
Kyburz, Andreas
Taube, Christian
Ottemann, Karen
van den Broek, Maries
Yousefi, Shida
Simon, Hans-Uwe
Müller, Anne
author_facet Arnold, Isabelle C.
Artola-Borán, Mariela
Tallón de Lara, Paulino
Kyburz, Andreas
Taube, Christian
Ottemann, Karen
van den Broek, Maries
Yousefi, Shida
Simon, Hans-Uwe
Müller, Anne
author_sort Arnold, Isabelle C.
collection PubMed
description Eosinophils are predominantly known for their contribution to allergy. Here, we have examined the function and regulation of gastrointestinal eosinophils in the steady-state and during infection with Helicobacter pylori or Citrobacter rodentium. We find that eosinophils are recruited to sites of infection, directly encounter live bacteria, and activate a signature transcriptional program; this applies also to human gastrointestinal eosinophils in humanized mice. The genetic or anti–IL-5–mediated depletion of eosinophils results in improved control of the infection, increased inflammation, and more pronounced Th1 responses. Eosinophils control Th1 responses via the IFN-γ–dependent up-regulation of PD-L1. Furthermore, we find that the conditional loss of IFN-γR in eosinophils phenocopies the effects of eosinophil depletion. Eosinophils further possess bactericidal properties that require their degranulation and the deployment of extracellular traps. Our results highlight two novel functions of this elusive cell type and link it to gastrointestinal homeostasis and anti-bacterial defense.
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spelling pubmed-60809072019-02-06 Eosinophils suppress Th1 responses and restrict bacterially induced gastrointestinal inflammation Arnold, Isabelle C. Artola-Borán, Mariela Tallón de Lara, Paulino Kyburz, Andreas Taube, Christian Ottemann, Karen van den Broek, Maries Yousefi, Shida Simon, Hans-Uwe Müller, Anne J Exp Med Research Articles Eosinophils are predominantly known for their contribution to allergy. Here, we have examined the function and regulation of gastrointestinal eosinophils in the steady-state and during infection with Helicobacter pylori or Citrobacter rodentium. We find that eosinophils are recruited to sites of infection, directly encounter live bacteria, and activate a signature transcriptional program; this applies also to human gastrointestinal eosinophils in humanized mice. The genetic or anti–IL-5–mediated depletion of eosinophils results in improved control of the infection, increased inflammation, and more pronounced Th1 responses. Eosinophils control Th1 responses via the IFN-γ–dependent up-regulation of PD-L1. Furthermore, we find that the conditional loss of IFN-γR in eosinophils phenocopies the effects of eosinophil depletion. Eosinophils further possess bactericidal properties that require their degranulation and the deployment of extracellular traps. Our results highlight two novel functions of this elusive cell type and link it to gastrointestinal homeostasis and anti-bacterial defense. Rockefeller University Press 2018-08-06 /pmc/articles/PMC6080907/ /pubmed/29970473 http://dx.doi.org/10.1084/jem.20172049 Text en © 2018 Arnold et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Arnold, Isabelle C.
Artola-Borán, Mariela
Tallón de Lara, Paulino
Kyburz, Andreas
Taube, Christian
Ottemann, Karen
van den Broek, Maries
Yousefi, Shida
Simon, Hans-Uwe
Müller, Anne
Eosinophils suppress Th1 responses and restrict bacterially induced gastrointestinal inflammation
title Eosinophils suppress Th1 responses and restrict bacterially induced gastrointestinal inflammation
title_full Eosinophils suppress Th1 responses and restrict bacterially induced gastrointestinal inflammation
title_fullStr Eosinophils suppress Th1 responses and restrict bacterially induced gastrointestinal inflammation
title_full_unstemmed Eosinophils suppress Th1 responses and restrict bacterially induced gastrointestinal inflammation
title_short Eosinophils suppress Th1 responses and restrict bacterially induced gastrointestinal inflammation
title_sort eosinophils suppress th1 responses and restrict bacterially induced gastrointestinal inflammation
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6080907/
https://www.ncbi.nlm.nih.gov/pubmed/29970473
http://dx.doi.org/10.1084/jem.20172049
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