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J Exp Med. 2018 Nov 5;215(11):2936-2954. doi: 10.1084/jem.20181210. Epub 2018 Oct 24.

Peyer's patch myeloid cells infection by Listeria signals through gp38+ stromal cells and locks intestinal villus invasion.

Author information

1
Institut Pasteur, Biology of Infection Unit, Paris, France.
2
Institut National de la Santé et de la Recherche Médicale U1117, Paris, France.
3
Institut Pasteur, Stroma, Inflammation and Tissue Repair Unit, Paris, France.
4
Institut National de la Santé et de la Recherche Médicale U1224, Paris, France.
5
Institut Pasteur, Innate Immunity Unit, Paris, France.
6
Institut National de la Santé et de la Recherche Médicale U1223, Paris, France.
7
Institut Pasteur, Microenvironnement and Immunity Unit, Paris, France.
8
Institut Pasteur, Human Histopathology and Animal Models Unit, Paris, France.
9
Institut Pasteur, Biology of Infection Unit, Paris, France marc.lecuit@pasteur.fr.
10
Paris Descartes University, Department of Infectious Diseases and Tropical Medicine, Necker-Enfants Malades University Hospital, APHP, Institut Imagine, Paris, France.

Abstract

The foodborne pathogen Listeria monocytogenes (Lm) crosses the intestinal villus epithelium via goblet cells (GCs) upon the interaction of Lm surface protein InlA with its receptor E-cadherin. Here, we show that Lm infection accelerates intestinal villus epithelium renewal while decreasing the number of GCs expressing luminally accessible E-cadherin, thereby locking Lm portal of entry. This novel innate immune response to an enteropathogen is triggered by the infection of Peyer's patch CX3CR1+ cells and the ensuing production of IL-23. It requires STAT3 phosphorylation in epithelial cells in response to IL-22 and IL-11 expressed by lamina propria gp38+ stromal cells. Lm-induced IFN-γ signaling and STAT1 phosphorylation in epithelial cells is also critical for Lm-associated intestinal epithelium response. GC depletion also leads to a decrease in colon mucus barrier thickness, thereby increasing host susceptibility to colitis. This study unveils a novel innate immune response to an enteropathogen, which implicates gp38+ stromal cells and locks intestinal villus invasion, but favors colitis.

PMID:
30355616
PMCID:
PMC6219733
[Available on 2019-05-05]
DOI:
10.1084/jem.20181210

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