Porphyromonas gingivalis-Epithelial Cell Interactions in Periodontitis

Porphyromonas gingivalis-Epithelial Cell Interactions in Periodontitis
2006
E. Andrian, D. Grenier*, and M. Rouabhia
Journal of Dental Research

© 2006 International and American Associations for Dental Research

Groupe de Recherche en Öcologie Buccale, Facult» de m»decine dentaire, Universit» Laval, Quebec City, Quebec, Canada, G1K 7P4

* corresponding author, Daniel.Grenier@greb.ulaval.ca

ABSTRACT

Emerging data on the consequences of the interactions between invasive oral bacteria and host cells have provided new insights into the pathogenesis of periodontal disease. Indeed, modulation of the mucosal epithelial barrier by pathogenic bacteria appears to be a critical step in the initiation and progression of periodontal disease. Periodontopathogens such as Porphyromonas gingivalis have developed different strategies to perturb the structural and functional integrity of the gingival epithelium. P. gingivalis adheres to, invades, and replicates within human epithelial cells. Adhesion of P. gingivalis to host cells is multimodal and involves the interaction of bacterial cell-surface adhesins with receptors expressed on the surfaces of epithelial cells. Internalization of P. gingivalis within host cells is rapid and requires both bacterial contact-dependent components and host-induced signaling pathways. P. gingivalis also subverts host responses to bacterial challenges by inactivating immune cells and molecules and by activating host processes leading to tissue destruction. The adaptive ability of these pathogens that allows them to survive within host cells and degrade periodontal tissue constituents may contribute to the initiation and progression of periodontitis. In this paper, we review current knowledge on the molecular cross-talk between P. gingivalis and gingival epithelial cells in the development of periodontitis.

KEY WORDS: periodontitis Ô epithelial cell Ô Porphyromonas gingivalis Ô adhesion Ô invasion

(I) INTRODUCTION

Periodontal disease is a complex multifactorial disorder involving Gram-negative anaerobic bacteria and host cell interactions, the combined effects of which lead to the destruction of tooth-supporting tissue. More specifically, periodontitis results from chronic inflammation of the gingiva and occurs by its spread into the deeper structures of the periodontium, leading to progressive destruction of periodontal tissues, including the alveolar bone (Williams, 1990). Approximately 15% of the population is affected by severe forms of the disease, which, if untreated, may result in tooth loss and systemic complications (American Academy of Periodontology, 1996). In addition, periodontitis has been associated with cardiovascular disease and pre-term delivery of low-birthweight infants (Teng et al., 2002). The progression of periodontitis is episodic, with active and inactive phases of tissue destruction, which reflects the opposing actions of bacterial challenges and host immune responses. The intimate interactions between periodontopathogens and host cells have become the subject of intensive investigations.

Porphyromonas gingivalis is a Gram-negative black-pigmented strict anaerobic bacterium that has been implicated as a major etiologic agent in the development and progression of periodontitis, more particularly, the chronic form (Lamont and Jenkinson, 1998; Holt et al., 1999). P. gingivalis produces a broad array of potential virulence factors involved in tissue colonization and destruction as well as in host defense perturbation (Holt et al., 1999). P. gingivalis is in close contact with the epithelium in periodontal pockets in vivo (Noiri et al., 1997) and can invade various cell lines, including epithelial cells (Sandros et al., 1994; Lamont et al., 1995; Belton et al., 1999; Rudney et al., 2001), endothelial cells (Deshpande et al., 1998; Dorn et al., 2000), and fibroblasts (Amornchat et al., 2003). The gingival epithelium is a stratified squamous epithelium that is an interface between the external environment, which is exposed to bacterial challenges, and the underlying periodontal tissue. The basal layer of the gingival epithelium is separated from and attached to the connective tissue by the basement lamina. The gingival epithelium can be divided into oral, sulcular, and junctional epithelia, based on their architecture. The sulcular epithelium, which extends from the oral epithelium to the gingival sulcus facing the teeth, and the junctional epithelium, which mediates the attachment of teeth to gingiva, are not keratinized, in contrast to the oral gingival epithelium. The sulcular and the coronal margins of the junctional epithelium are in close contact with bacteria in the gingival sulcus and appear to be crucial sites with regard to the development of periodontal diseases. During periodontitis, loss of connective tissue attachment and bone resorption associated with the formation of periodontal pockets is related to the pathologic conversion of the junctional and the sulcular epithelium to a pocket epithelium. Invasion of mammalian epithelial cells is an important strategy developed by pathogenic bacteria to evade the host immune system and cause tissue damage. Gingival epithelial cells are the primary physical barrier to infections by periodontopathogens in vivo. While the epithelium was previously thought to be passive, Dale (2002) proposed a new perspective, assigning an active role to the epithelium in the host response to bacterial infections. The epithelium reacts to bacterial challenges by signaling host responses and integrating innate and acquired immune responses. This review focuses on the current understanding of host epithelial cell-P. gingivalis interactions in the pathogenesis of periodontitis.

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