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Gastroenterology. 2015 Jun;148(7):1417-26. doi: 10.1053/j.gastro.2015.02.053. Epub 2015 Mar 4.

γδ Intraepithelial Lymphocyte Migration Limits Transepithelial Pathogen Invasion and Systemic Disease in Mice.

Author information

1
Department of Pathology, The University of Chicago, Chicago, Illinois.
2
Department of Ophthalmology and Visual Sciences, The University of Chicago, Chicago, Illinois; Department of Pediatrics, The University of Chicago, Chicago, Illinois.
3
Department of Medicine, The University of Chicago, Chicago, Illinois; Section of Pulmonary and Critical Care, The University of Chicago, Chicago, Illinois. Electronic address: asperlin@medicine.bsd.uchicago.edu.
4
Department of Pathology, The University of Chicago, Chicago, Illinois; Department of Medicine, The University of Chicago, Chicago, Illinois. Electronic address: jturner@bsd.uchicago.edu.

Abstract

BACKGROUND & AIMS:

Intraepithelial lymphocytes that express the γδ T-cell receptor (γδ IELs) limit pathogen translocation across the intestinal epithelium by unknown mechanisms. We investigated whether γδ IEL migration and interaction with epithelial cells promote mucosal barrier maintenance during enteric infection.

METHODS:

Salmonella typhimurium or Toxoplasma gondii were administered to knockout (KO) mice lacking either the T cell receptor δ chain (Tcrd) or CD103, or control TcrdEGFP C57BL/6 reporter mice. Intravital microscopy was used to visualize migration of green fluorescent protein (GFP)-tagged γδ T cells within the small intestinal mucosa of mice infected with DsRed-labeled S typhimurium. Mixed bone marrow chimeras were generated to assess the effects of γδ IEL migration on early pathogen invasion and chronic systemic infection.

RESULTS:

Morphometric analyses of intravital video microscopy data showed that γδ IELs rapidly localized to and remained near epithelial cells in direct contact with bacteria. Within 1 hour, greater numbers of T gondii or S typhimurium were present within mucosae of mice with migration-defective occludin KO γδ T cells, compared with controls. Pathogen invasion in Tcrd KO mice was quantitatively similar to that in mice with occludin-deficient γδ T cells, whereas invasion in CD103 KO mice, which have increased migration of γδ T cells into the lateral intercellular space, was reduced by 63%. Consistent with a role of γδ T-cell migration in early host defense, systemic salmonellosis developed more rapidly and with greater severity in mice with occludin-deficient γδ IELs, relative to those with wild-type or CD103 KO γδ IELs.

CONCLUSIONS:

In mice, intraepithelial migration to epithelial cells in contact with pathogens is essential to γδ IEL surveillance and immediate host defense. γδ IEL occludin is required for early surveillance that limits systemic disease.

KEYWORDS:

Host Defense; Intestinal Epithelium; T cell; Tight Junction

PMID:
25747597
PMCID:
PMC4685713
DOI:
10.1053/j.gastro.2015.02.053
[Indexed for MEDLINE]
Free PMC Article

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