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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 (2018). Eosinophils suppress Th1 responses and restrict bacterially induced gastrointestinal inflammation. Journal of Experimental Medicine, 215(8):2055-2072.

Abstract

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 or 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.

Abstract

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 or 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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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Molecular Cancer Research
07 Faculty of Science > Institute of Molecular Cancer Research
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Uncontrolled Keywords:Immunology, Immunology and Allergy
Language:English
Date:3 July 2018
Deposited On:11 Jul 2018 11:55
Last Modified:31 Aug 2018 23:51
Publisher:Rockefeller University Press
ISSN:0022-1007
OA Status:Green
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1084/jem.20172049
PubMed ID:29970473
Project Information:
  • : FunderSNSF
  • : Grant ID31003A_152851
  • : Project TitleThe impact of radio- and immunotherapy on local tumor-specific immunity

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