Vibrio parahaemolyticus Flagellin Stimulates the Maturation of Human Monocyte-Derived Dendritic Cells and Elicits Th1-Type Immune Response.

Abstract

Flagellin, the principal component of bacterial flagella, interacts with Toll-like receptor (TLR5) and induces the generation of a pro-inflammation response and activation of host dendritic cells (DCs) in vivo. In this study, we investigated the role of Vibrio parahaemolyticus (V. parahaemolyticus)-derived flagellin as a DC maturation-inducing molecule. V. parahemolyticus-derived flagellin (100–1,000 ng/ml) induced the maturation of human monocyte-derived dendritic cells in a concentration-dependent manner with maximal effect at 500 ng/ml of flagellin as determined by increased levels of surface markers, namely, CD1a, CD80, CD86, CD83, and HLA-DR, a response which could be compared with the phenotypic change in immature DCs (iDCs) treated with lipopolysaccharide (LPS) or cytokine cocktails (CC) with TNF-α, IL-1β, IL-6, and PGE2. Moreover, V. parahaemolyticus-derived flagellin also reduced phagocytic activity, and increased IL-12 production in a polymyxin B-insensitive manner and DC-mediated T cell proliferation, which is comparable with that of LPS- or CC-treated iDCs at several responder to stimulator ratios, suggesting the functional maturation of DCs by V. parahaemolyticus-derived flagellin. Maturation of DCs by V. parahaemolyticus-derived flagellin also elicited a significant increase in specific cytotoxic activity against target cells at several effector to target cells ratios as determined by 51Cr-release assay, and induced Th1-type immune response, such as increase in INF-γ producing cells, determined by ELISPOT assay and analysis of intracellular cytokine staining assay. Taken together, this study demonstrates the role of V. parahaemolyticus-derived flagellin in the functional maturation of DCs, and suggests that V. parahaemolyticus-derived flagellin as a useful molecule for the development of a DC-based immunotherapy against tumors.