However, significantly more IFN-gamma was produced by m-MDDC of CP compared to HP selleck screening library subjects after S. sanguinis and P. intermedia stimulation (p = 0.006 and 0.009, respectively; Student’s unpaired t-test) ( Fig. 4), with significantly more IFN-gamma produced in response to P. intermedia stimulation than to S. sanguinis ( Fig. 4). Maturation of MDDCs is accompanied by decreased CD1a and increased cell surface expression of MHC class II (HLA-DR), and co-stimulatory molecules such as CD80 and CD86, which enable antigen presentation and activation of naïve CD4+ and CD8+ T cells, thus promoting the adaptive immune response.16 We found that expression of HLA-DR and CD11c

were lower in m-MDDCs from CP than HP individuals. In contrast, CD1a and CD123 expression were higher in m-MDDCs than in individuals with periodontitis. These results suggest that differentiation and subsequent maturation of bacterial-unstimulated or bacterially stimulated DCs may be defective in CP individuals, and thus may have their differentiation driven towards pDCs. pDCs express low levels of HLA-DR and co-stimulatory molecules (in agreement with our results) and high level of CD123 molecule and are unable to stimulate antigen-specific T cell proliferation.5 The role of pDCs in periodontitis has not been described. Because CD4+ T helper cells must interact with mature DCs to acquire effector

function,17 the lower MDDC maturation and skewing towards pDC differentiation in periodontitis may impair antigen presentation and stimulation of an anti-bacterial response learn more in periodontal tissue. This possibility is supported by our findings with P. intermedia. P. intermedia is the predominant bacteria early in the biofilm, with P. gingivalis and T. denticola becoming more dominant later. Thus, defective DC maturation may already occur

in individuals with CP before the colonization of the biofilm by more virulent bacteria. To date, studies of periodontal bacteria heptaminol effects on DC maturation have yielded contrasting results; there have been reports of both upregulation and downregulation of MDDCs by the bacterium P. gingivalis. 9, 10, 11, 12 and 17 These conflicting results may be due in part to the use of different microbial components or to differences in the immunological profiles of the hosts in these studies. In fact, expression of mfa-1 and fimA fimbriae on P. gingivalis negatively and positively, respectively, mediates MDDC maturation. 19 Furthermore, strain-specific immune response was induced by three P. gingivalis strains, A7A1-28, W83 and W50. Strains W50 and W83 were shown to induce alveolar bone loss and expression of high levels of interleukin-4 (IL-4), whereas the A7A1-28 strain did not significantly promote bone resorption in mice and stimulated increased IL-10. 20 We found that expression of co-stimulatory molecules on m-MDDC from HP and CP patients was differentially regulated by the bacteria. P.