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.
Highlights
Epithelial cells and dendritic cells (DCs) both initiate and contribute to innate immune responses to bacteria
Human defensin expression in DCs in vitro and in vivo To determine whether DCs express β-defensins, we compared the absolute gene expression levels in the absence of bacteria between unstimulated Immature DCs (iDCs) and gingival epithelial cells (GECs) by quantitative real-time PCR using corresponding defensin plasmids as a standard curve
The expression level of hBD3 was much higher than that of hBD2 in GECs, while hBD2 expression was higher than that of hBD3 in DCs. Both GECs and DCs express detectable levels of β-defensins, the level is much lower in DCs
Summary
Epithelial cells and dendritic cells (DCs) both initiate and contribute to innate immune responses to bacteria. The β-defensins are antimicrobial peptides that are widely expressed in epithelial tissues including the oral cavity [5,6,7] They have a broad spectrum of activity against both Gram-negative and Gram-positive bacteria as well as some fungi and viruses [2,8]. The expression of the inducible hBD2 in GECs in vitro is regulated by several distinct signaling pathways, depending on the oral bacterial species Commensal bacteria such as Fusobacterium nucleatum and Streptococcus gordonii induce hBD2 via MAPK pathways, while periodontal pathogens such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans signal via NF-κB; in addition, P. gingivalis signals via protease-activated receptors [16,17,18,19]. Purified bacterial LPS is a poor stimulant for hBD2, and in vitro studies show that hBD2 induction is greatly amplified in epithelial cells when monocyte/macrophage-like cells are included in the culture system [20,21]
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