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

ABSTRACT: Intraepithelial lymphocytes that express the ?? T-cell receptor (?? IELs) limit pathogen translocation across the intestinal epithelium by unknown mechanisms. We investigated whether ?? IEL migration and interaction with epithelial cells promote mucosal barrier maintenance during enteric infection.Salmonella typhimurium or Toxoplasma gondii were administered to knockout (KO) mice lacking either the T cell receptor ? chain (Tcrd) or CD103, or control TcrdEGFP C57BL/6 reporter mice. Intravital microscopy was used to visualize migration of green fluorescent protein (GFP)-tagged ?? 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 ?? IEL migration on early pathogen invasion and chronic systemic infection.Morphometric analyses of intravital video microscopy data showed that ?? 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 ?? T cells, compared with controls. Pathogen invasion in Tcrd KO mice was quantitatively similar to that in mice with occludin-deficient ?? T cells, whereas invasion in CD103 KO mice, which have increased migration of ?? T cells into the lateral intercellular space, was reduced by 63%. Consistent with a role of ?? T-cell migration in early host defense, systemic salmonellosis developed more rapidly and with greater severity in mice with occludin-deficient ?? IELs, relative to those with wild-type or CD103 KO ?? IELs.In mice, intraepithelial migration to epithelial cells in contact with pathogens is essential to ?? IEL surveillance and immediate host defense. ?? IEL occludin is required for early surveillance that limits systemic disease.

SUBMITTER: Edelblum KL 

PROVIDER: S-EPMC4685713 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature