title: Soluble flagellin coimmunization attenuates Th1 priming to Salmonella and clearance by modulating dendritic cell activation and cytokine production.
abstract: Soluble flagellin (sFliC) from Salmonella Typhimurium (STm) can induce a Th2 response to itself and coadministered antigens through ligation of TLR5. These properties suggest that sFliC could potentially modulate responses to Th1 antigens like live STm if both antigens are given concurrently. After coimmunization of mice with sFliC and STm there was a reduction in Th1 T cells (T-bet(+) IFN-γ(+) CD4 T cells) compared to STm alone and there was impaired clearance of STm. In contrast, there was no significant defect in the early extrafollicular B-cell response to STm. These effects are dependent upon TLR5 and flagellin expression by STm. The mechanism for these effects is not related to IL-4 induced to sFliC but rather to the effects of sFliC coimmunization on DCs. After coimmunization with STm and sFliC, splenic DCs had a lower expression of costimulatory molecules and profoundly altered kinetics of IL-12 and TNFα expression. Ex vivo experiments using in vivo conditioned DCs confirmed the effects of sFliC were due to altered DC function during a critical window in the coordinated interplay between DCs and naïve T cells. This has marked implications for understanding how limits in Th1 priming can be achieved during infection-induced, Th1-mediated inflammation.
authors.affiliation: Division of Immunity and Infection, Institute of Biomedical Research, University of Birmingham, Birmingham, UK.
authors.forename: Adriana
authors.initials: A
authors.lastname: Flores-Langarica
authors.affiliation: Division of Immunity and Infection, Institute of Biomedical Research, University of Birmingham, Birmingham, UK.
authors.forename: Saeeda
authors.initials: S
authors.lastname: Bobat
authors.affiliation: Division of Immunity and Infection, Institute of Biomedical Research, University of Birmingham, Birmingham, UK.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Marshall
authors.affiliation: Deparamento de Biologia Celular. CINVESTAV. Mexico, D.F. Mexico.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Yam-Puc
authors.affiliation: Division of Immunity and Infection, Institute of Biomedical Research, University of Birmingham, Birmingham, UK.
authors.forename: Charlotte N
authors.initials: CN
authors.lastname: Cook
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Karine
authors.initials: K
authors.lastname: Serre
authors.affiliation: The Institute of Food Research, Norwich Research Park, Norwich, UK.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kingsley
authors.affiliation: Deparamento de Biologia Celular. CINVESTAV. Mexico, D.F. Mexico.
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Flores-Romo
authors.affiliation: International Research and Development Centre for Mucosal Vaccine, Institute for Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Uematsu
authors.affiliation: Laboratory of Host Defense, World Premier International Immunology Frontier Research Center, Osaka University, Suita Osaka, Japan.|Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita Osaka, Japan.
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.affiliation: Division of Immunity and Infection, Institute of Biomedical Research, University of Birmingham, Birmingham, UK.
authors.forename: Ian R
authors.initials: IR
authors.lastname: Henderson
authors.affiliation: Division of Immunity and Infection, Institute of Biomedical Research, University of Birmingham, Birmingham, UK.
authors.forename: Kai M
authors.initials: KM
authors.lastname: Toellner
authors.affiliation: Division of Immunity and Infection, Institute of Biomedical Research, University of Birmingham, Birmingham, UK.
authors.forename: Adam F
authors.initials: AF
authors.lastname: Cunningham
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D005408:Flagellin / Q000235:genetics / Q000276:immunology*; D007114:Immunization; D051379:Mice; D018345:Mice, Knockout; D012480:Salmonella Infections / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology; D051198:Toll-Like Receptor 5 / Q000235:genetics / Q000276:immunology
chemical_list: D016207:Cytokines; D051198:Toll-Like Receptor 5; D005408:Flagellin
keywords: Dendritic cell activation; Flagellin; Priming; Salmonella Typhimurium; Th1 cells