This result suggests that the P intermedia lysate may be more im

This result suggests that the P. intermedia lysate may be more immunogenic and then induce stronger immune response and more periodontal destruction or the bacterium may be more efficiently eliminated by the response in CP individuals. P. gingivalis has been considered more virulent than P. intermedia, 21 which is supported by the differential

regulation of CD80 and CD86 by P. intermedia and P. gingivalis. In CP individuals, downregulation of either CD80 or CD86 by S. sanguinis, T. denticola, and P. gingivalis may be part of an immune evasion strategy or, in the case of S. sanguinis, may induce tolerance. Upregulation of co-stimulatory molecule expression on B cells find more has been described in periodontal disease. 22 On average, we found that the ratio of bacterial lysate-induced production of IL-10 to IL-12 was 3-fold greater in the supernatants of m-MDDCs from HP compared to CP subjects. IL-10 exerts

an anti-inflammatory effect by reducing the production of inflammatory cytokines (including IL-12) and controlling periodontal bone loss.23 Thus, the tendency of the periodontal bacteria to downregulate IL-10 and upregulate IL-12p70 levels may contribute to poor control of inflammation and increased periodontal tissue destruction in CP subjects. Although the higher expression of IL-12 but lower maturation of DCs in CP patients might seem somewhat contradictory, we suggest that it is not. We speculate that MDDCs from periodontitis individuals may show a more Natural Product Library in vivo activated basal state, which help to explain why some subjects are more prone to develop periodontitis. IL-12p70 plays a key role in bacterial clearance through the induction of IFN-gamma, which in turn activates

the bactericidal function of macrophages.25 We found that P. intermedia induced more IL-12p70 and IFN-gamma production by m-MDDC of CP subjects Protirelin than did other bacteria, and thus P. intermedia may be more efficiently eliminated from the host. S. sanguinis also stimulated more IFN-gamma production by CP than HP m-MDDC co-cultured with T cells. The higher IFN-gamma response in CP subjects compared to HP may mediate a stronger and more destructive inflammatory response. However, the latter explanation may be unlikely as Jotwani et al. found that IFN-gamma levels are not increased significantly in chronic periodontitis patients. 10 In conclusion, we show here that m-MDDC from periodontitis subjects differed from those of healthy subjects by exhibiting a more immature phenotype and cytokine profile biased towards a pro-inflammatory response, without increasing IL-10 production. These results clearly indicate a dysregulated immune response in these subjects. This pattern was maintained/exacerbated when cells were stimulated by P. intermedia, P gingivalis, T. denticola, and S. sanguinis. P.

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