title: TLR1-induced chemokine production is critical for mucosal immunity against Yersinia enterocolitica.
abstract: Our gastrointestinal tract is a portal of entry for a number of bacteria and viruses. Thus, this tissue must develop ways to induce antigen-specific T cell and antibody responses quickly. Intestinal epithelial cells are a central player in barrier function and also in communicating signals from invading pathogens to the underlying immune tissue. Here we demonstrate that activation of Toll-like receptor 1 (TLR1) in the epithelium leads to the upregulation of the chemokine CCL20 during oral infection with Yersinia enterocolitica. Further, both neutralization of CCL20 using polyclonal antibody treatment and deletion of TLR1 resulted in a defect in CCR6+ dendritic cells (DCs), which produce innate cytokines that help to induce anti-Yersinia-specific T helper 17 (TH17) cells and IgA production. These data demonstrate a novel role for TLR1 signaling in the intestinal epithelium and demonstrate that together TLR1 and CCL20 are critical mediators of TH17 immunity through the activation and recruitment of DCs.
authors: Department of Biomedical Sciences, Midwestern University, Downers Grove, Illinois, USA.
authors: Y
authors: Y
authors: Sugiura
authors: K
authors: K
authors: Kamdar
authors: S
authors: S
authors: Khakpour
authors: G
authors: G
authors: Young
authors: W J
authors: WJ
authors: Karpus
authors: R William
authors: RW
authors: DePaolo
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D000917:Antibody Formation / Q000187:drug effects; D002478:Cells, Cultured; D054418:Chemokine CCL20 / Q000276:immunology*; D018925:Chemokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D018928:Immunity, Mucosal / Q000187:drug effects; D007070:Immunoglobulin A / Q000097:blood; D007413:Intestinal Mucosa / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054399:Receptors, CCR6 / Q000378:metabolism; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology*; D051194:Toll-Like Receptor 1 / Q000276:immunology*; D015009:Yersinia Infections / Q000276:immunology*; D015008:Yersinia enterocolitica / Q000276:immunology*
chemical_list: D019138:Antibodies, Blocking; D054418:Chemokine CCL20; D018925:Chemokines; D007070:Immunoglobulin A; D054399:Receptors, CCR6; D051194:Toll-Like Receptor 1