Porphyromonas gingivalis fimbriae dampen P2X7-dependent interleukin-1ß secretion.
J Innate Immun
; 6(6): 831-45, 2014.
Article
em En
| MEDLINE
| ID: mdl-24925032
ABSTRACT
Porphyromonas 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)-1ß synthesis but not mature IL-1ß secretion, unless the P2X7 receptor is activated by extracellular ATP (eATP). Here, we investigated the role of P. gingivalis fimbriae in eATP-induced IL-1ß 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-1ß secretion after eATP stimulation compared to 381 in WT BMDMs, but not in P2X7-deficient cells. This mechanism was dependent on K(+) efflux and Ca(2+)-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-1ß was Toll-like receptor 2 and MyD88 dependent, and not associated with fimbria expression. Fimbria-dependent down-modulation of IL-1ß 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-1ß secretion is impaired by P. gingivalis fimbriae in a P2X7-dependent manner.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Infecções por Bacteroidaceae
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Porphyromonas gingivalis
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Fímbrias Bacterianas
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Interleucina-1beta
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Receptores Purinérgicos P2X7
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Macrófagos
Limite:
Animals
Idioma:
En
Revista:
J Innate Immun
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Brasil