Our human in situ studies indicate that dendritic cells (DC), the most potent antigen presenting cells, infiltrate gingiva and particularly, the T cell rich lamina propria during chronic periodontitis (Jotwani et al. 2001). The fimbriae of P.gingivalis (Pg) enables it to invade many cell types, but its role in DC invasion and modulation of immunostimulatory function is unclear. Objectives: To determine the role of Pg fimbriae in invasion of DCs and in their immunostimulatory functions. Methods: Monocyte-derived DCs or control monocytes (MC) were pulsed with either fluorescent-labeled Pg 381 or fimbriae-deficient mutant DPG-3. Cytospin slides were prepared at 1,2, 4, and 18hrs to follow the kinetics of bacterial uptake. At 18hrs, cell surface markers of DCs and MC were evaluated by four color immunofluorescence staining using FACS and autologous T cell proliferation assay (uptake of tritiated thymidine). DC and T cell cytokines (IL-1beta, TNF-alpha, IL-10, IL-12, IL-2, IL-4, IL-6, IL-8 and IFN-gamma) in culture supernatants were detected by cytometric bead array kit. Results: Fimbriated Pg 381 was efficiently internalized by DCs, gaining access to 50-60% of DCs in 18 hrs, while DPG3 was poorly taken up (10-15% DCs). Entry into monocytes was comparable. Pg 381-pulsed DCs showed better maturation (increase in CD83 expression), higher upregulation of accessory molecules (CD80, 86, HLA-DR), higher levels of inflammatory cytokines and the chemokine IL-8, and induced a more potent T cell response (proliferation and release of IFN-gamma) as compared to DPG3-pulsed DCs or Pg381- pulsed MC. Conclusions: Pg fimbriae appears to be essential for efficient uptake of Pg by DCs and for the ability of DCs to induce an immunostimulatory Th1-type response. Supported by NIH/NIDCR DE14160-01 and DE13154-01