In:
Journal of Innate Immunity, S. Karger AG, Vol. 6, No. 6 ( 2014), p. 831-845
Abstract:
〈 i 〉 Porphyromonas gingivalis 〈 /i 〉 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 〈 i 〉 P. gingivalis 〈 /i 〉 fimbriae in eATP-induced IL-1β release. Bone marrow-derived macrophages (BMDMs) from wild-type (WT) or P2X7-deficient mice were infected with 〈 i 〉 P. gingivalis 〈 /i 〉 (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 〈 sup 〉 + 〈 /sup 〉 efflux and Ca 〈 sup 〉 2+ 〈 /sup 〉 -independent phospholipase A 〈 sub 〉 2 〈 /sub 〉 activity. Accordingly, non-fimbriated 〈 i 〉 P. gingivalis 〈 /i 〉 failed to inhibit apoptosis via the eATP/P2X7 pathway. Furthermore, 〈 i 〉 P. gingivalis 〈 /i 〉 -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 〈 i 〉 P. gingivalis 〈 /i 〉 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 〈 i 〉 P. gingivalis 〈 /i 〉 fimbriae in a P2X7-dependent manner.
Type of Medium:
Online Resource
ISSN:
1662-811X
,
1662-8128
Language:
English
Publisher:
S. Karger AG
Publication Date:
2014
detail.hit.zdb_id:
2455818-7
