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Transepithelial movement of intestinal pathogens is limited by γδ IEL occludin‐dependent migration
Author(s) -
Edelblum Karen L,
Singh Gurminder,
McLeod Rima,
Turner Jerrold R
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.131.2
Subject(s) - occludin , biology , microbiology and biotechnology , microfold cell , toxoplasma gondii , immunology , intraepithelial lymphocyte , tight junction , immune system , antibody
Intraepithelial lymphocytes (IELs) expressing the γδ T cell receptor migrate extensively within the intestinal epithelium, which is primarily dependent on γδ IEL‐expressed occludin. Intravital microscopy was used to determine if enteric infection alters γδ IEL migration. Mucosal application of DsRed‐labeled Salmonella typhimurium (SL3201, 10 8 CFU) increased γδ IEL migration into the epithelial lateral intercellular space by 19%, particularly at sites of bacterial adhesion. Thus, we hypothesized that γδ IEL migration contributes to early innate immunity at mucosal surfaces. To assess the role of occludin‐dependent γδ IEL migration, mixed bone marrow chimeras were generated by engrafting irradiated hosts with γδ T cell‐deficient marrow (80%) with either wildtype GFPγδ or occludin knockout GFPγδ marrow (20%). Within 30 min, chimeras with occludin‐deficient γδ T cells displayed 3‐fold increases in S. typhimurium translocation relative to chimeras with occludin‐sufficient γδ T cells. Similarly, γδ IEL occludin‐deficiency increased Toxoplasma gondii (PRU, 10 cysts) translocation 1h after oral infection 3.5‐fold. In each case, pathogen invasion in chimeras with occludin‐deficient γδ T cells was similar to that in mice completely deficient in γδ T cells. These data show that occludin expression by γδ IELs is an important mediator of innate host defense, likely due to the role of occludin in γδ IEL migration.