title: Early MyD88-dependent induction of interleukin-17A expression during Salmonella colitis.
abstract: The development of T helper 17 (T(H)17) cells is a well-established adaptive mechanism for the production of interleukin-17A (IL-17A), a cytokine involved in neutrophil recruitment. However, pathways contributing to mucosal expression of IL-17A during the initial phase of a bacterial infection have received less attention. Here we used the mouse colitis model of Salmonella enterica serotype Typhimurium infection to investigate the contribution of myeloid differentiation primary response protein 88 (MyD88) to inflammation and mucosal IL-17A expression. Expression of IL-23 in the cecal mucosa during S. Typhimurium colitis was dependent on the presence of MyD88. Furthermore, initial expression of IL-17A at 24 h after S. Typhimurium infection was dependent on MyD88 and the receptor for IL-1β. IL-23 and IL-1β synergized in inducing expression of IL-17A in splenic T cells in vitro. In the intestinal mucosa, IL-17A was produced by three distinct T cell populations, including δγ T cells, T(H)17 cells, and CD4(-)CD8(-) T cells. The absence of IL-1β signaling or IL-17 signaling reduced CXC chemokine expression but did not alter the overall severity of pathological lesions in the cecal mucosa. In contrast, cecal pathology and neutrophil recruitment were markedly reduced in Myd88-deficient mice during the initial phases of S. Typhimurium infection. Collectively, these data demonstrate that MyD88-dependent mechanisms, including an initial expression of IL-17A, are important for orchestrating early inflammatory responses during S. Typhimurium colitis.
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, One Shields Ave., Davis, CA 95616-8645, USA.
authors.forename: A Marijke
authors.initials: AM
authors.lastname: Keestra
authors.forename: Ivan
authors.initials: I
authors.lastname: Godinez
authors.forename: Mariana N
authors.initials: MN
authors.lastname: Xavier
authors.forename: Maria G
authors.initials: MG
authors.lastname: Winter
authors.forename: Sebastian E
authors.initials: SE
authors.lastname: Winter
authors.forename: Renée M
authors.initials: RM
authors.lastname: Tsolis
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Bäumler
mesh_terms: D000818:Animals; D002432:Cecum / Q000276:immunology / Q000382:microbiology; D002460:Cell Line; D003092:Colitis / Q000276:immunology / Q000382:microbiology / Q000473:pathology / Q000662:veterinary*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006651:Histocytochemistry; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008853:Microscopy; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology / Q000378:metabolism*; D012376:Rodent Diseases / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D012481:Salmonella Infections, Animal / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D012486:Salmonella typhimurium / Q000276:immunology* / Q000472:pathogenicity*; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: C098680:Il17a protein, mouse; D020381:Interleukin-17; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88