Human dendritic cells respond to Porphyromonas gingivalis LPS by promoting a Th2 effector response in vitro

Abstract

Understanding how mucosal pathogens modulate the immune response may facilitate the development of vaccines for disparate human diseases. In the present study, human monocyte-derived DC (MDDC) were pulsed with LPS of the oral pathogen Porphyromonas gingivalis and Escherichia coli 25922 and analyzed for: (i) production of Th-biasing/inflammatory cytokines; (ii) maturation/costimulatory molecules; and (iii) induction of allogeneic CD4 + and naive CD45RA + T cell proliferation and release of Th1 or Th2 cytokines. We show that E. coli LPS-pulsed MDDC released Th1-biasing cytokines -consisting of high levels of IL-12 p70, IFN-+ -inducible protein 10 (IP-10) -but also TNF- § , IL-10, IL-6 and IL-1 g . In contrast, no IL-12 p70 or IP-10, and lower levels of TNF- § and IL-10 were induced by P. gingivalis LPS. These differences were sustained at LPS doses that yielded nearly equivalent maturation of MDDC; moreover the T cell response was consistent: E. coli LPS-pulsed MDDC induced higher T cell proliferation, and T cells released more IFN-+ and IL-2, but less IL-5 than T cells co-cultured with P. gingivalis LPS pulsed-MDDC. IL-13 was secreted by naive CD45RA + CD45RO -CD4 + T cells in response to P. gingivalisLPS-pulsed MDDC. These results suggest that human MDDC can be polarized by LPS from the mucosal pathogen P. gingivalis to induce a Th2 effector response in vitro.

T Cell Response Mediated by Myeloid Cell-Derived IL-12 Is Responsible for Porphyromonas gingivalis-Induced Periodontitis in IL-10-Deficient Mice

“…Moreover, preimmunization of BALB/c mice with P. gingivalis in the presence of IL-12 resulted in enhanced P. gingivalis-specific T cell proliferation, a strongly polarized Th1 immune response including IFN-␥ production, and the induction of severe periapical bone loss (43). Although P. gingivalis LPS has been reported to induce Th2 effector responses in dendritic cells (44), costimulation of dendritic cells with P. gingivalis LPS and IFN-␥ significantly enhanced both p35 and p40 IL-12 mRNA, while failing to up-regulate IL-10 mRNA (45). Thus, distinct patterns of polarization of the T cell response may be induced by P. gingivalis LPS compared with infection with the live organism.…”

Medical biofilms

“…P. gingivalis also expresses unique immunosuppressive LPS (Cohen et al, 2004;Jotwani et al, 2003;Pulendran et al, 2001) and proteolytic gingipains (Potempa et al, 2003). LPS of P. gingivalis, relative to those of Escherichia coli, stimulate dendritic cells to secrete IL-10, but not IL-12, in vitro (Jotwani et al, 2003) and in vivo (Pulendran et al, 2001).…”

“…P. gingivalis also expresses unique immunosuppressive LPS (Cohen et al, 2004;Jotwani et al, 2003;Pulendran et al, 2001) and proteolytic gingipains (Potempa et al, 2003). LPS of P. gingivalis, relative to those of Escherichia coli, stimulate dendritic cells to secrete IL-10, but not IL-12, in vitro (Jotwani et al, 2003) and in vivo (Pulendran et al, 2001). These two factors (sub-optimal DC maturation and truncated cytokine expression) leads to the induction of a Th2-effector response, which suggests that P. gingivalis may target dendritic cell C-type lectin receptors (e.g., dendritic cell-specific ICAM-3-grabbing non-integrins) for entry, and for blunting of dendritic cell maturation.…”

Human IL‐19 regulates immunity through auto‐induction of IL‐19 and production of IL‐10

“…This exciting observation demonstrates a clear regulatory role for IL-19: the modulation of DC function. IL-10-rich DC are found in chronic inflammatory environments, such as the periodontal lesion [35][36][37]. These IL-10 + DC are thought to skew the T cell response towards the Th2 type.…”