Porphyromonas gingivalis fimbriae dampen P2X7-dependent interleukin-1β secretion

Ana Carolina Morandini, Erivan S. Ramos-Junior, Jan Potempa, Ky Anh Nguyen, Ana Carolina Oliveira, Maria Bellio, David M. Ojcius, Julio Scharfstein, Robson Coutinho-Silva

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Porphyromonas gingivalis is a major contributor to the patho-genesis 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. gingiva-lis 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 A 2 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-stimu-lated 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 fim-briae in a P2X7-dependent manner.

Original languageEnglish (US)
Pages (from-to)831-845
Number of pages15
JournalJournal of Innate Immunity
Volume6
Issue number6
DOIs
StatePublished - Nov 7 2014
Externally publishedYes

Keywords

  • Interleukin-1β
  • Macrophages
  • P2X7 receptor
  • Porphyromonas gingivalis

ASJC Scopus subject areas

  • Immunology and Allergy

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