Intestinal Epithelial and Intraepithelial T Cell Crosstalk Mediates a Dynamic Response to Infection

Intestinal intraepithelial lymphocytes (IELs) are located at the critical interface between the intestinal lumen, which is chronically exposed to food and microbes, and the core of the body. Using high-resolution microscopy techniques and intersectional genetic tools, we investigated the nature of I...

Full description

Saved in:
Bibliographic Details
Published in:Cell 2017-11, Vol.171 (4), p.783-794.e13
Main Authors: Hoytema van Konijnenburg, David P., Reis, Bernardo S., Pedicord, Virginia A., Farache, Julia, Victora, Gabriel D., Mucida, Daniel
Format: Article
Language:English
Subjects:
Animals
Epithelial Cells - metabolism
gammadelta glycolysis
IELs
Immunologic Surveillance
Intestinal Mucosa - immunology
intestine
Intestines - cytology
Intestines - immunology
lymphocytes
Mice
microbiota
mucosal imaging
multiphoton
myd88
Salmonella Infections - immunology
Salmonella Infections - microbiology
Salmonella typhimurium - physiology
T-Lymphocytes - immunology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Intestinal intraepithelial lymphocytes (IELs) are located at the critical interface between the intestinal lumen, which is chronically exposed to food and microbes, and the core of the body. Using high-resolution microscopy techniques and intersectional genetic tools, we investigated the nature of IEL responses to luminal microbes. We observed that TCRγδ IELs exhibit unique microbiota-dependent location and movement patterns in the epithelial compartment. This behavioral pattern quickly changes upon exposure to different enteric pathogens, resulting in increased interepithelial cell (EC) scanning, expression of antimicrobial genes, and glycolysis. Both dynamic and metabolic changes to γδ IEL depend on pathogen sensing by ECs. Direct modulation of glycolysis is sufficient to change γδ IEL behavior and susceptibility to early pathogen invasion. Our results uncover a coordinated EC-IEL response to enteric infections that modulates lymphocyte energy utilization and dynamics and supports maintenance of the intestinal epithelial barrier. [Display omitted] [Display omitted] •γδ IELs display microbe-dependent localization and motility patterns•Infection induces rapid behavioral changes in γδ IELs•Coordinated epithelial cell-IEL responses to pathogens are EC-Myd88 dependent•EC responses to microbial cues trigger a protective IEL metabolic switch Communication between epithelial cells and intraepithelial lymphocytes guides lymphocyte energy utilization and dynamic behavior, helping to support maintenance of the intestinal epithelial barrier during infections.
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2017.08.046