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Science. 2019 Mar 8;363(6431). pii: eaat4042. doi: 10.1126/science.aat4042.

Endocytosis of commensal antigens by intestinal epithelial cells regulates mucosal T cell homeostasis.

Author information

1
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
2
Department of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
3
Department of Biological Sciences, Rutgers University, Newark, NJ 07102, USA.
4
Department of Pharmacology, Physiology and Neurosciences, Rutgers University, Newark, NJ 07103, USA.
5
Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
6
RIKEN Center for Integrative Medical Sciences, Kanagawa 230-0045, Japan.
7
Department of Medicine, Division of Gastroenterology, Jichi Medical University, Tochigi 329-0498, Japan.
8
Department of Biochemistry & Biomedical Sciences, Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada.
9
Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo 160-8582, Japan.
10
Department of Microbiology and Immunology and The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, New York, NY 10065, USA.
11
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. bjorkman@caltech.edu ii2137@cumc.columbia.edu.
12
Department of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. bjorkman@caltech.edu ii2137@cumc.columbia.edu.
#
Contributed equally

Abstract

Commensal bacteria influence host physiology, without invading host tissues. We show that proteins from segmented filamentous bacteria (SFB) are transferred into intestinal epithelial cells (IECs) through adhesion-directed endocytosis that is distinct from the clathrin-dependent endocytosis of invasive pathogens. This process transfers microbial cell wall-associated proteins, including an antigen that stimulates mucosal T helper 17 (TH17) cell differentiation, into the cytosol of IECs in a cell division control protein 42 homolog (CDC42)-dependent manner. Removal of CDC42 activity in vivo led to disruption of endocytosis induced by SFB and decreased epithelial antigen acquisition, with consequent loss of mucosal TH17 cells. Our findings demonstrate direct communication between a resident gut microbe and the host and show that under physiological conditions, IECs acquire antigens from commensal bacteria for generation of T cell responses to the resident microbiota.

PMID:
30846568
PMCID:
PMC6708280
[Available on 2020-03-08]
DOI:
10.1126/science.aat4042
[Indexed for MEDLINE]

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