TLR4 signaling via MyD88 and TRIF differentially shape the CD4+ T cell response to Porphyromonas gingivalis hemagglutinin B

Academic Article

Abstract

  • Recombinant hemagglutinin B (rHagB), a virulence factor of the periodontal pathogen Porphyromonas gingivalis, has been shown to induce protective immunity against bacterial infection. Furthermore, we have demonstrated that rHagB is a TLR4 agonist for dendritic cells. However, it is not known how rHagB dendritic cell stimulation affects the activation and differentiation of T cells. Therefore, we undertook the present study to examine the role of TLR4 signaling in shaping the CD4+ T cell response following immunization of mice with rHagB. Immunization with this Ag resulted in the induction of specific CD4+ T cells and Ab responses. In TLR4-/- and MyD88 -/- but not Toll/IL-1R domain-containing adapter inducing IFN-β-deficient (TRIFLps2) mice, there was an increase in the Th2 CD4+ T cell subset, a decrease in the Th1 subset, and higher serum IgG1/IgG2 levels of HagB-specific Abs compared with those in wild-type mice. These finding were accompanied by increased GATA-3 and Foxp3 expression and a decrease in the activation of CD4+ T cells isolated from TLR4-/- and MyD88-/- mice. Interestingly, TLR4-/- CD4+ T cells showed an increase in IL-2/STAT5 signaling. Whereas TRIF deficiency had minimal effects on the CD4+ T cell response, it resulted in increased IFN-γ and IL-17 production by memory CD4+ T cells. To our knowledge, these results demonstrate for the first time that TLR4 signaling, via the downstream MyD88 and TRIF molecules, exerts a differential regulation on the CD4+ T cell response to HagB Ag. The gained insight from the present work will aid in designing better therapeutic strategies against P. gingivalis infection. Copyright © 2011 by The American Association of Immunologists, Inc.
  • Published In

    Digital Object Identifier (doi)

    Author List

  • Gaddis DE; Michalek SM; Katz J
  • Start Page

  • 5772
  • End Page

  • 5783
  • Volume

  • 186
  • Issue

  • 10