Objectives: Primary immune responses are initiated by dendritic cells (DCs), which inform naive T helper (Th) cells about invading pathogens. DCs settle as interstitial DCs and Langerhans cells in peripheral non-lymphoid tissues including gingiva. These peripheral DCs capture and process Ag at the site of inflammation, and then migrate to lymph nodes to prime Th cells. DCs undergo a series of events leading to irreversible maturation upon stimulation with invading bacteria, and up-regulate cytokine production and surface molecule expression with different kinetics. To investigate the responses DCs during periodontal infection, we analyzed the effects of lipopolysaccharides (LPS) from Porphyromonas gingivalis on the phenotype of human peripheral blood DCs (PBDCs). Methods: PBDCs were generated by culturing plastic-adherent mononuclear cells in the presence of IL-4 and GM-CSF. DCs were incubated with graded doses of P. gingivalis 381 LPS or Escherichia coli LPS. The expression of various surface molecules was analyzed using a flowcytometer. Cytokine production was measured by ELISA. Results: P. gnigivalis LPS preferentially up-regulated CD14 and CD16 expression on immature PBDCs (CD14^-CD16^-), although E. coli LPS did not alter the expression of these molecules. P. gingivalis LPS-induced CD14⁺CD16⁺cells expressed dendritic cell markers: CD40, CD80, CD1a and HLA-DR. However, CD83 expression was lower than E. coli LPS-stimulated DCs. P. gnigivalis LPS was a weaker stimulator in terms of IL-6, IL-8, IL-10, IL-12, MCP-1 and RANTES production from DC as compared to E. coli LPS. Both LPS stimulated-DC induced comparable allogenic T cell proliferation. Conclusions: These results suggestively indicated P. gnigivalis LPS trigger a maturation of DC with unique characteristics, that modulate immune responses occurred at the site of periodontal infection. P. gingivalis-induced CD14⁺CD16⁺ DC subsets may contribute to induction of chronic inflammation. Supported by in part by Grant-in-Aid for Scientific Research (No.12470469 and No.13557187) from JSPS.

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