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Infection and Immunity, March 2004, p. 1725-1732, Vol. 72, No. 3
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.3.1725-1732.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Fimbriated Porphyromonas gingivalis Is More Efficient than Fimbria-Deficient P. gingivalis in Entering Human Dendritic Cells In Vitro and Induces an Inflammatory Th1 Effector Response

Ravi Jotwani and Christopher W. Cutler*

Department of Periodontics, School of Dental Medicine, Stony Brook University, Stony Brook, New York 11794-8703

Received 3 October 2003/ Returned for modification 15 November 2003/ Accepted 4 December 2003

Porphyromonas gingivalis is a fimbriated mucosal pathogen implicated in chronic periodontitis (CP). The fimbriae are required for invasion of the gingival mucosa and for induction of CP in animal models of periodontitis. CP is associated with infection of immature dendritic cells (DCs) by P. gingivalis in situ and with increased numbers of dermal DCs (DDCs) and mature DCs in the lamina propria. The role of fimbriae in gaining entry into human DCs and how this modulates the inflammatory and effector immune responses, however, have not been explored. To address this, we generated monocyte-derived DCs (MDDCs) in vitro which phenotypically and functionally resemble DDCs. We show here that virulent fimbriated P. gingivalis 381, in contrast to its fimbria-deficient mutant, P. gingivalis DPG3, efficiently gains entry to MDDCs in a manner dependent on active cell metabolism and cytoskeletal rearrangement. In addition, uptake of 381, unlike DPG3, induces DCs to undergo maturation, upregulate costimulatory molecules, and secrete inflammation cytokines interleukin-1ß (IL-1ß), IL-6, tumor necrosis factor alpha, IL-10, and IL-12. Moreover, MDDCs pulsed with 381 also stimulated a higher autologous mixed lymphocyte reaction and induced a Th1-type response, with gamma interferon (IFN-{gamma}) being the main cytokine. Monocytes used as controls demonstrated fimbria-dependent uptake of 381 as well but produced low levels of inflammatory cytokines compared to MDDCs. When MDDCs were pulsed with recombinant fimbrillin of P. gingivalis (10 µg/ml), maturation of MDDCs was also induced; moreover, matured MDDCs induced proliferation of autologous CD4+ T cells and release of IFN-{gamma}. Thus, these results establish the significance of P. gingivalis fimbriae in the uptake of P. gingivalis by MDDCs and in induction of immunostimulatory Th1 responses.

* Corresponding author. Mailing address: Department of Periodontics, School of Dental Medicine, Stony Brook University, Stony Brook, NY 11794-8703. Phone: (631) 632-3025. Fax: (631) 632-3113. E-mail: ccutler{at}notes.cc.sunysb.edu.

Editor: J. T. Barbieri

Infection and Immunity, March 2004, p. 1725-1732, Vol. 72, No. 3
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.3.1725-1732.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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