TY - JOUR
T1 - P2X7 receptor-mediated leukocyte recruitment and Porphyromonas gingivalis clearance requires IL-1β production and autocrine IL-1 receptor activation
AU - Almeida-da-Silva, Cássio Luiz Coutinho
AU - Ramos-Junior, Erivan S.
AU - Morandini, Ana Carolina
AU - Rocha, Gabrielle da Costa
AU - Marinho, Ygor
AU - Tamura, Augusto Shuiti
AU - de Andrade, Kívia Queiroz
AU - Bellio, Maria
AU - Savio, Luiz Eduardo Baggio
AU - Scharfstein, Julio
AU - Ojcius, David M.
AU - Coutinho-Silva, Robson
N1 - Publisher Copyright:
© 2018 Elsevier GmbH
PY - 2019/1
Y1 - 2019/1
N2 - 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.
AB - 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.
KW - IL-1 receptor
KW - IL-1β
KW - Inflammasome
KW - P2X7 receptor
KW - Porphyromonas gingivalis
UR - http://www.scopus.com/inward/record.url?scp=85056537858&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85056537858&partnerID=8YFLogxK
U2 - 10.1016/j.imbio.2018.10.008
DO - 10.1016/j.imbio.2018.10.008
M3 - Article
C2 - 30429052
AN - SCOPUS:85056537858
SN - 0171-2985
VL - 224
SP - 50
EP - 59
JO - Immunobiology
JF - Immunobiology
IS - 1
ER -