Eosinophils suppress Th1 responses and restrict bacterially induced gastrointestinal inflammation
Open Access
- 1 August 2018
- journal article
- research article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 215 (8), 2055-2072
- https://doi.org/10.1084/jem.20172049
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 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-gamma-dependent up-regulation of PD-L1. Furthermore, we find that the conditional loss of IFN-gamma R 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.Funding Information
- Swiss National Science Foundation (BSCGIO_157841/1)
- Swiss National Science Foundation (31003A_152851)
- Oncosuisse (KFS-3233-08-2013)
- University of Zurich
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