Differential and coordinated expression of defensins and cytokines by gingival epithelial cells and dendritic cells in response to oral bacteria

Abstract

BackgroundEpithelial cells and dendritic cells (DCs) both initiate and contribute to innate immune responses to bacteria. However, much less is known about the coordinated regulation of innate immune responses between GECs and immune cells, particularly DCs in the oral cavity. The present study was conducted to investigate whether their responses are coordinated and are bacteria-specific in the oral cavity.ResultsThe β-defensin antimicrobial peptides hBD1, hBD2 and hBD3 were expressed by immature DCs as well as gingival epithelial cells (GECs). HBD1, hBD2 and hBD3 are upregulated in DCs while hBD2 and hBD3 are upregulated in GECs in response to bacterial stimulation. Responses of both cell types were bacteria-specific, as demonstrated by distinctive profiles of hBDs mRNA expression and secreted cytokines and chemokines in response to cell wall preparations of various bacteria of different pathogenicity: Fusobacterium nucleatum, Actinomyces naeslundii and Porphyromonas gingivalis. The regulation of expression of hBD2, IL-8, CXCL2/GROβ and CCL-20/MIP3α by GECs was greatly enhanced by conditioned medium from bacterially activated DCs. This enhancement was primarily mediated via IL-1β, since induction was largely attenuated by IL-1 receptor antagonist. In addition, the defensins influence DCs by eliciting differential cytokine and chemokine secretion. HBD2 significantly induced IL-6, while hBD3 induced MCP-1 to approximately the same extent as LPS, suggesting a unique role in immune responses.ConclusionsThe results suggest that cytokines, chemokines and β-defensins are involved in interaction of these two cell types, and the responses are bacteria-specific. Differential and coordinated regulation between GECs and DCs may be important in regulation of innate immune homeostasis and response to pathogens in the oral cavity.

Effect of Smoking on the Expression of Human Beta-Defensin-2 in Gingival Crevicular Fluid after Non Surgical Periodontal Therapy

“…With the bacterial invasion, β-defensins stimulate the secretion of chemokines, such as IL-8 and MCP-1, from dendritic cells, and, also, act as chemoattractants, which bring phagocytes and lymphocytes to the site of infection. Correspondingly, the activated immune response limits innate response and, hence, secretion of β-defensins (42) . Our findings were in agreement with previous studies shown that smoking downregulates hβD-2 expression (37,39,43) .…”

Defensins and their role in the maintenance of the oral cavity homeostasis – a literature review

“…Like in the other human body regions, the expression of HBD-1 in the oral mucosa cells occurs constantly. The basal HBD-2 concentration in the oral epithelium is relatively low, but increases rapidly in the presence of cytokines (TNF-α and IL-1β), bacteria (Fusobacterium nucleatum, Porphyromonas gingivalis) and fungi (Candida albicans) [12,18,20,28]. In the non-oral epithelium the HBD-2 expression occurs only in the case of inflammation or infection.…”

Oral Epithelial Cytokines

“…Cytokines and chemokines are involved in the interaction between gum epithelial cell and dendritic cells (DCs). The responses are bacterio-specific differential and coordinated regulation between gingival EC and DCs may be important in regulation of innate hemostasis and responses to pathogens in the oral cavity [1]. Polymorph nuclear cell induce protective type TH1 cytokines epithelial response in an in-vitro model of oral candidiasis [16].…”

“…Among these influences epithelial cell produced cytokines and chemokines [1]. The aim of the present mini-review is confined onto the oral epithelial cytokines.…”