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Infection and Immunity, July 2004, p. 3743-3751, Vol. 72, No. 7
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.7.3743-3751.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Activation of the Phosphatidylinositol 3-Kinase/Akt Pathway Contributes to Survival of Primary Epithelial Cells Infected with the Periodontal Pathogen Porphyromonas gingivalis

Özlem Yilmaz,1* Thomas Jungas,2 Philippe Verbeke,2 and David M. Ojcius2,3

Department of Pathobiology, University of Washington, Seattle, Washington 98195,1 Université Paris 7, Institut Jacques Monod, CNRS UMR 7592, 75251 Paris Cedex 5, France,2 School of Natural Sciences, University of California, Merced, California 953443

Received 23 February 2004/ Returned for modification 22 March 2004/ Accepted 26 March 2004

Porphyromonas gingivalis, an important periodontal pathogen, infects primary gingival epithelial cells (GECs). Despite the large number of bacteria that replicate inside the GECs, the host cell remains viable. We demonstrate that P. gingivalis triggers rapid and reversible surface phosphatidylserine exposure through a mechanism requiring caspase activation. However, after 1 day of infection, the bacteria no longer induce phosphatidylserine externalization and instead protect infected cells against apoptosis. Infection exerts its effect at the level of mitochondria, as P. gingivalis also blocks depolarization of the mitochondrial transmembrane potential and cytochrome c release. Interestingly, protein kinase B/Akt is phosphorylated during infection, which can be blocked with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. Suppression of the PI3K/Akt pathway following staurosporine treatment results in mitochondrial-membrane depolarization, cytochrome c release, DNA fragmentation, and increased apoptosis of infected GECs. Thus, P. gingivalis stimulates early surface exposure of phosphatidylserine, which could downmodulate the inflammatory response, while also promoting host cell survival through the PI3K/Akt pathway.

* Corresponding author. Mailing address: Department of Pathobiology, University of Washington, School of Public Health, HSC Box 357238, Seattle, WA 98195. Phone: (206) 543-6427. Fax: (206) 543-3873. E-mail: ozlem{at}u.washington.edu.

Editor: D. L. Burns

Infection and Immunity, July 2004, p. 3743-3751, Vol. 72, No. 7
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.7.3743-3751.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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