Porphyromonas gingivalis fimbriae dampen P2X7-dependent interleukin-1β secretionJournal of Innate Immunity
ORCiDDavid M. Ojcius: 0000-0003-1461-4495
AbstractPorphyromonas gingivalis is a major contributor to the pathogenesis of periodontitis, an infection-driven inflammatory disease that leads to bone destruction. This pathogen stimulates pro-interleukin (IL)-1β synthesis but not mature IL-1β secretion, unless the P2X7 receptor is activated by extracellular ATP (eATP). Here, we investigated the role of P. gingivalis fimbriae in eATP-induced IL-1β release. Bone marrow-derived macrophages (BMDMs) from wild-type (WT) or P2X7-deficient mice were infected with P. gingivalis (381) or isogenic fimbria-deficient (DPG3) strain with or without subsequent eATP stimulation. DPG3 induced higher IL-1β secretion after eATP stimulation compared to 381 in WT BMDMs, but not in P2X7-deficient cells. This mechanism was dependent on K+ efflux and Ca2+-independent phospholipase A2 activity. Accordingly, non-fimbriated P. gingivalis failed to inhibit apoptosis via the eATP/P2X7 pathway. Furthermore, P. gingivalis-driven stimulation of IL-1β was Toll-like receptor 2 and MyD88 dependent, and not associated with fimbria expression. Fimbria-dependent down-modulation of IL-1β was selective, as levels of other cytokines remained unaffected by P2X7 deficiency. Confocal microscopy demonstrated the presence of discrete P2X7 expression in the absence of P. gingivalis stimulation, which was enhanced by 381-stimulated cells. Notably, DPG3-infected macrophages revealed a distinct pattern of P2X7 receptor expression with a marked focus formation. Collectively, these data demonstrate that eATP-induced IL-1β secretion is impaired by P. gingivalis fimbriae in a P2X7-dependent manner.
Citation InformationA. C. Morandini, E. S. Ramos-Junior, J. Potempo, K. A. Nguyen, et al.. "Porphyromonas gingivalis fimbriae dampen P2X7-dependent interleukin-1β secretion" Journal of Innate Immunity Vol. 6 Iss. 6 (2014) p. 831 - 845 ISSN: 1662-811X
Available at: http://works.bepress.com/david-ojcius/180/