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Article
Porphyromonas gingivalis attenuates ATP-mediated inflammasome activation and HMGB1 release through expression of a nucleoside-diphosphate kinase
Microbes and Infection
  • Larry Johnson, University of California, Merced
  • Kalina R. Atanasova, University of Florida
  • Phuong Q. Bui, University of California, Merced
  • Jungnam Lee, University of Florida
  • Shu-Chen Hung, University of California, Merced
  • Özlem Yilmaz, University of Florida
  • David M. Ojcius, University of California, Merced
ORCiD
David M. Ojcius: 0000-0003-1461-4495
Document Type
Article
DOI
10.1016/j.micinf.2015.03.010
Publication Date
5-1-2015
Abstract
Many intracellular pathogens evade the innate immune response in order to survive and proliferate within infected cells. We show that Porphyromonas gingivalis, an intracellular opportunistic pathogen, uses a nucleoside-diphosphate kinase (NDK) homolog to inhibit innate immune responses due to stimulation by extracellular ATP, which acts as a danger signal that binds to P2X7 receptors and induces activation of an inflammasome and caspase-1. Thus, infection of gingival epithelial cells (GECs) with wild-type P. gingivalis results in inhibition of ATP-induced caspase-1 activation. However, ndk-deficient P. gingivalis is less effective than wild-type P. gingivalis in reducing ATP-mediated caspase-1 activation and secretion of the pro-inflammatory cytokine, IL-1β, from infected GECs. Furthermore, P. gingivalis NDK modulates release of high-mobility group protein B1 (HMGB1), a pro-inflammatory danger signal, which remains associated with chromatin in healthy cells. Unexpectedly, infection with either wild-type or ndk-deficient P. gingivalis causes release of HMGB1 from the nucleus to the cytosol. But HMGB1 is released to the extracellular space when uninfected GECs are further stimulated with ATP, and there is more HMGB1 released from the cells when ATP-treated cells are infected with ndk-deficient mutant than wild-type P. gingivalis. Our results reveal that NDK plays a significant role in inhibiting P2X7-dependent inflammasome activation and HMGB1 release from infected GECs.
Citation Information
Larry Johnson, Kalina R. Atanasova, Phuong Q. Bui, Jungnam Lee, et al.. "Porphyromonas gingivalis attenuates ATP-mediated inflammasome activation and HMGB1 release through expression of a nucleoside-diphosphate kinase" Microbes and Infection Vol. 17 Iss. 5 (2015) p. 369 - 377 ISSN: 1286-4579
Available at: http://works.bepress.com/david-ojcius/179/