Bacillus anthracis cell wall peptidoglycan activates human dendritic cells to promote naïve TH17 and TFH cell differentiation (P4207)

Abstract

Abstract In cutaneous and inhalational Bacillus anthracis infection, innate responses by tissue dendritic cells (DC) will direct adaptive immunity. To dissect these responses, human DCs were incubated with killed vegetative bacteria or highly purified cell wall peptidoglycan (PGN) of the B. anthracis ΔSterne strain. Both vegetative bacteria and PGN stimulated the activation of human DCs, which involved upregulation of surface HLA-DR, the T cell costimulatory molecules CD40 and CD86, the lymph node homing chemokine receptor CCR7, and CD83. B. anthracis PGN and vegetative bacteria elicited production of TNFα, IL-6, and IL-23, but not IL-12p70 or IL-10. To determine the effect of this cytokine profile on CD4+ T cell differentiation, we compared the ability of B. anthracis PGN- and Escherichia coli LPS-stimulated DCs to induce the differentiation of naïve CD4+ T cells into T helper (TH) subsets. While LPS-exposed DCs induced the polarization of CD4+ T cells into TH1 cells producing IFNγ, PGN-exposed DCs directed the differentiation of TH17 cells producing IL-17. Exposure of DCs to either PGN or LPS induced TFH cells producing IL-21. In sum, B. anthracis PGN is a highly stimulatory cell wall component that activates human DCs to display T cell costimulatory molecules and secrete IL-6 and IL-23. Thus, in vivo, PGN-exposed DCs are likely to promote the differentiation of proinflammatory TH17 cells important for extracellular bacteria infections and TFH cells important for humoral immunity.