Activation of NLRP3 and AIM2 inflammasomes by Porphyromonas gingivalis infection.


Porphyromonas gingivalis, a major periodontopathogen, is involved in the pathogenesis of periodontitis. Interleukin-1β (IL-1β), a proinflammatory cytokine, regulates innate immune responses and is critical for the host defense against bacterial infection. However, excessive IL-1β is linked to periodontal destruction. IL-1β synthesis, maturation, and secretion are tightly regulated by Toll-like receptor (TLR) signaling and inflammasome activation. We found much higher levels of inflammasome components in the gingival tissues from patients with chronic periodontitis than in those from healthy controls. To investigate the molecular mechanisms by which P. gingivalis infection causes IL-1β secretion, we examined the characteristics of P. gingivalis-induced signaling in differentiated THP-1 cells. We found that P. gingivalis induces IL-1β secretion and inflammatory cell death via caspase-1 activation. We also found that P. gingivalis-induced IL-1β secretion and pyroptic cell death required both NLRP3 and AIM2 inflammasome activation. The activation of the NLRP3 inflammasome was mediated by ATP release, the P2X7 receptor, and lysosomal damage. In addition, we found that the priming signal via TLR2 and TLR4 activation precedes P. gingivalis-induced IL-1β release. Our study provides novel insight into the innate immune response against P. gingivalis infection which could potentially be used for the prevention and therapy of periodontitis.

DOI: 10.1128/IAI.00862-13
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@article{Park2014ActivationON, title={Activation of NLRP3 and AIM2 inflammasomes by Porphyromonas gingivalis infection.}, author={Eunjoo Park and Hee Sam Na and Yu-Ri Song and Seong Yeol Shin and You-Me Kim and Jin Chung}, journal={Infection and immunity}, year={2014}, volume={82 1}, pages={112-23} }