P2X7 receptor-mediated leukocyte recruitment and Porphyromonas gingivalis clearance requires IL-1β production and autocrine IL-1 receptor activation

Cássio Luiz Coutinho Almeida-da-Silva, Erivan S. Ramos-Junior, Ana Carolina Morandini, Gabrielle da Costa Rocha, Ygor Marinho, Augusto Shuiti Tamura, Kívia Queiroz de Andrade, Maria Bellio, Luiz Eduardo Baggio Savio, Julio Scharfstein, David M. Ojcius, Robson Coutinho-Silva

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

The Gram-negative bacterium Porphyromonas gingivalis is strongly associated with periodontitis. We previously demonstrated that P2X7 receptor activation by extracellular ATP (eATP) triggers elimination of intracellular pathogens, such as Leishmania amazonensis, Toxoplasma gondii and Chlamydia trachomatis. We also showed that eATP-induced IL-1β secretion via the P2X7 receptor is impaired by P. gingivalis fimbriae. Furthermore, enhanced P2X7 receptor expression was detected in the maxilla of P. gingivalis-orally infected mice as well as in human periodontitis patients. Here, we examined the effect of P2X7-, caspase-1/11- and IL-1 receptor-mediated responses during P. gingivalis infection. P2X7 receptor played a large role in controlling P. gingivalis infection and P. gingivalis-induced recruitment of inflammatory cells, especially neutrophils. In addition, IL-1β secretion was detected at different time points only when P2X7 receptor was expressed and in the presence of eATP treatment ex vivo. Activation of P2X7 receptor and IL-1 receptor by eATP and IL-1β, respectively, promoted P. gingivalis elimination in macrophages. Interestingly, eATP-induced P. gingivalis killing was inhibited by the IL-1 receptor antagonist (IL-1RA), consistent with autocrine activation of the IL-1 receptor for P. gingivalis elimination. In vivo, caspase-1/11 and IL-1 receptor were also required for bacterial clearance, leukocyte recruitment and IL-1β production after P. gingivalis infection. Our data demonstrate that the P2X7-IL-1 receptor axis activation is required for effective innate immune responses against P. gingivalis infection.

Original languageEnglish (US)
Pages (from-to)50-59
Number of pages10
JournalImmunobiology
Volume224
Issue number1
DOIs
StatePublished - Jan 2019
Externally publishedYes

Keywords

  • IL-1 receptor
  • IL-1β
  • Inflammasome
  • P2X7 receptor
  • Porphyromonas gingivalis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Hematology

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