Vibrio vulnificus infection induces the maturation and activation of dendritic cells with inflammatory Th17-polarizing ability.

Abstract

Vibrio vulnificus (V.vulnificus) is a gram-negative bacterium, which causes life-threatening septicemia and gastroenteritis through the consumption of contaminated seafood or wound infection. In addition, V.vulnificus infection is known to stimulate the production of several pro-inflammatory cytokines, which are associated with inflammatory responses mediated predominantly by dendritic cells (DCs), functioning as antigen-presenting cells. The present study aimed to investigate whether V.vulnificus infection induced the maturation and activation of murine DCs, which have the ability to polarize Thelper (Th) cells into Th17 cells. Dysregulated Th17 cell responses are known to cause tissue damage, promoting the penetration of pathogens; however, Th17 cells are also involved in host defense against infection. Infection with V.vulnificus significantly increased the expression of cell surface molecules, including CD40, CD80 and major histocompatibility complex classII, leading to the maturation and activation of DCs. In the present study, the analysis of the cytokine profiles of DCs upon infection with V.vulnificus revealed the preferential production of interleukin-1β (IL-1β) and IL-6, through which V.vulnificus-infected DCs induced the polarization of Th17 cells when naïve CD4+ Tcells were co-incubated. The reduction of Th17 cell generation through the use of anti-IL-6 neutralizing antibodies indicated that the Th17-polarizing capacity of V.vulnificus was predominantly dependent on DC-derived IL-6. The invivo administration of V.vulnificus-infected DCs consistently increased the Th17 cell population in the lymph nodes of mice. Finally, the oral administration of V.vulnificus in mice also increased Th17 cell responses in the lamina propria of the small intestine. These results collectively demonstrated that V.vulnificus induced inflammatory Th17 cell responses via DCs, which may be associated with the immunopathological effects caused by V.vulnificus infection.