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

Authors

Cássio Luiz Coutinho Almeida-da-Silva, University of the PacificFollow
Erivan S. Ramos-Junior, University of the Pacific
Ana Carolina Morandini, University of the PacificFollow
Gabrielle da Costa Rocha, Universidade Federal do Rio de Janeiro
Ygor Marinho, Universidade Federal do Rio de Janeiro
Augusto Shuiti Tamura, Universidade Federal do Rio de Janeiro
Kívia Queiroz de Andrade, Universidade Federal do Rio de Janeiro
Maria Bellio, Universidade Federal do Rio de Janeiro
Luiz Eduardo Baggio Savio, Universidade Federal do Rio de Janeiro
Julio Scharfstein, Universidade Federal do Rio de Janeiro
David M. Ojcius, University of the Pacific, CaliforniaFollow
Robson Coutinho-Silva, Universidade Federal do Rio de Janeiro

ORCiD

David M. Ojcius: 0000-0003-1461-4495; Cassio Almeida-da-Silva: 0000-0001-9173-7208

Department

Biomedical Sciences

Document Type

Article

Publication Title

Immunobiology

ISSN

01712985

Volume

224

Issue

1

DOI

10.1016/j.imbio.2018.10.008

First Page

50

Last Page

59

Publication Date

1-1-2019

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.

Recommended Citation

Almeida-da-Silva, C. L., Ramos-Junior, E. S., Morandini, A. C., da Costa Rocha, G., Marinho, Y., Tamura, A. S., de Andrade, K. Q., Bellio, M., Savio, L. E., Scharfstein, J., Ojcius, D. M., & Coutinho-Silva, R. (2019). P2X7 receptor-mediated leukocyte recruitment and Porphyromonas gingivalis clearance requires IL-1β production and autocrine IL-1 receptor activation. Immunobiology, 224(1), 50–59. DOI: 10.1016/j.imbio.2018.10.008
https://scholarlycommons.pacific.edu/dugoni-facarticles/464