Differential regulation of immune responses by odontoblasts

Abstract

Odontoblasts (OBs) are cells lining the inner surface of the tooth. Their potential role in host defenses within the tooth is suggested by their production of antimicrobial beta-defensins, but their role needs confirmation. The present study sought to define the roles of human OBs in microbial recognition and innate host responses. Toll-like receptor 2 (TLR2) and TLR4, as well as CCR6, were immunolocalized in human OBs and their dentinal processes in situ. To examine OB function we used organotypic tooth crown cultures to maintain human OBs within their dentin scaffold. Cells in the OB layer of cultured and non-cultured crown preparations expressed mRNA for several markers of innate immunity including chemokine CCL20, chemokine receptor CCR6, TLR2, TLR4 and the OB marker dentin sialophosphoprotein (DSPP). Expression of human beta-defensin 1 (hBD1), hBD2, hBD3, interleukin-8 (IL-8), and CCL20 increased with time in culture. Tooth crown odontoblast (TcOB) cultures were stimulated with agonist that was specific for TLR2 (Pam3CSK4) or TLR4 [Escherichia coli lipopolysaccharide (LPS)]. Nuclear factor-kappaB assays confirmed the TLR2 activity of Pam3CSK4 and the TLR4 activity of LPS. LPS up-regulated IL-1beta, tumor necrosis factor-alpha (TNF-alpha), CCL20, hBD2, IL-8, TLR2 and TLR4; however, Pam3CSK4 down-regulated these mRNAs. IL-1beta, TNF-alpha, CCL20 were also up-regulated from six-fold to 30-fold in TcOB preparations from decayed teeth. Our results show for the first time that OBs express microbial pattern recognition receptors in situ, thus allowing differential responses to gram-positive and gram-negative bacteria, and suggest that pro-inflammatory cytokines and innate immune responses in decayed teeth may result from TLR4 signaling.

TGF-β1 Inhibits TLR-mediated Odontoblast Responses to Oral Bacteria

“…Odontoblasts establish the peripheral cellular layer of the dental pulp and extend their cellular processes into the tubular structure of dentin, such that they are the first cells able to detect signals from bacteria in the caries lesion and to respond to TGF-β1 in the dentin matrix. Odontoblasts express receptors for TGF-β1 (Smith et al, 1998;Sloan et al, 1999) and for microbes, Toll-like receptors (Veerayutthwilai et al, 2007).…”

The role of transforming growth factor beta in tertiary dentinogenesis

“…29 The main task of odontoblasts is to synthesize and secrete collagens and several non-collagenous proteins from which the dentin organic matrix is formed. Odontoblasts control dentin matrix mineralization by determining the nature of the extra cellular matrix and by controlling the influx of mineral ions.…”

The Role of Chemokines and Cytokines in the Pathogenesis of Periodontal and Periapical Lesions: Current Concepts

“…After dental tissue damage by caries lesions, odontoblasts are the first pulp cells to encounter both products of the infectious process, including the invading pathogens and their components, as well as detecting dentine matrix constituents released during demineralization. Although odontoblasts provide barrier function by protecting the underlying tissue from the invading bacteria, they are also immunocompetent and capable of coordinating an inflammatory response (Veerayutthwilai et al, 2007). Progression of the carious infection deeper into the underlying dental tissue results in changes in the composition of the bacterial biofilm (Takahashi et al, 2008) and also deleterious effects on the host cells, including death of pulp cells.…”