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J Immunol. 2019 Jul 15;203(2):532-543. doi: 10.4049/jimmunol.1800890. Epub 2019 May 29.

CRTAM Shapes the Gut Microbiota and Enhances the Severity of Infection.

Author information

1
Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093.
2
Department of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, CA 92697.
3
Institute for Immunology, University of California, Irvine, Irvine, CA 92697.
4
Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92697.
5
Department of Pathology and Laboratory Medicine, University of California, Irvine, Irvine, CA 92697.
6
Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093; manuelar@ucsd.edu.
7
Chiba University-University of California San Diego Center for Mucosal Immunology, Allergy, and Vaccines, La Jolla, CA 92093; and.
8
Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA 92093.

Abstract

Gut lymphocytes and the microbiota establish a reciprocal relationship that impacts the host immune response. Class I-restricted T cell-associated molecule (CRTAM) is a cell adhesion molecule expressed by intraepithelial T cells and is required for their retention in the gut. In this study, we show that CRTAM expression affects gut microbiota composition under homeostatic conditions. Moreover, Crtam-/- mice infected with the intestinal pathogen Salmonella exhibit reduced Th17 responses, lower levels of inflammation, and reduced Salmonella burden, which is accompanied by expansion of other microbial taxa. Thus, CRTAM enhances susceptibility to Salmonella, likely by promoting the inflammatory response that promotes the pathogen's growth. We also found that the gut microbiota from wild-type mice, but not from Crtam-/- mice, induces CRTAM expression and Th17 responses in ex-germ-free mice during Salmonella infection. Our study demonstrates a reciprocal relationship between CRTAM expression and the gut microbiota, which ultimately impacts the host response to enteric pathogens.

PMID:
31142601
PMCID:
PMC6615957
[Available on 2020-07-15]
DOI:
10.4049/jimmunol.1800890

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