Soluble flagellin coimmunization attenuates Th1 priming to Salmonella and clearance by modulating dendritic cell activation and cytokine production

Research output: Contribution to journalArticle

Authors

  • Juan Carlos Yam-puc
  • Charlotte N. Cook
  • Karine Serre
  • Robert A. Kingsley
  • Leopoldo Flores-romo
  • Satoshi Uematsu
  • Shizuo Akira
  • Adam Cunningham

External organisations

  • Deparamento de Biologia Celular. CINVESTAV. Mexico; D.F. Mexico
  • Instituto de Medicina Molecular; Faculdade de Medicina, Universidade de Lisboa; Lisbon Portugal
  • The Institute of Food Research; Norwich Research Park; Norwich UK
  • International Research and Development Centre for Mucosal Vaccine; Institute for Medical Science; The University of Tokyo; Tokyo Japan
  • 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

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.

Details

Original languageEnglish
Pages (from-to)2299-2311
JournalEuropean Journal of Immunology
Volume45
Issue number8
Early online date24 Jun 2015
Publication statusPublished - 7 Aug 2015

Keywords

  • Dendritic cell activation, Flagellin, Priming, Salmonella Typhimurium, Th1 cells