Insertional Inactivation ofpacandrmlBGenes Reduces the Release of Tumor Necrosis Factor Alpha, Interleukin-6, and Interleukin-8 Induced byStreptococcus mutansin Monocytic, Dental Pulp, and Periodontal Ligament Cells

Abstract

Streptococcus mutans possesses different cell wall molecules, such as protein of the I/II family, the serotype f polysaccharide rhamnose glucose polymer (RGP), and lipoteichoic acid (LTA), which act as adhesins and modulins, allowing S. mutans to colonize teeth and cause dental caries and pulpitis. We tested several isogenic mutants of S. mutans defective in protein I/II and/or RGP, as well as purified modulins such as protein I/II, RGP, and LTA, for their binding and activation abilities on monocytic, dental pulp (DP), and periodontal ligament (PDL) cells. Our results demonstrate that both protein I/II and RGP play important roles in streptococcal adherence to human monocytic and fibroblastic cells, whereas LTA is only a minor adhesin. In the activation process, the cytokine response elicited is polarized toward a Th1 response which seems principally due to protein I/II and RGP. Even if protein I/II seems to be more efficient in its purified form in triggering cells to release interleukin-8 (IL-8), RGP is the most efficient cytokine-stimulating component in intact bacteria, while LTA plays only a minor role. In cell activation, we showed, by using either cytochalasin D or coated ligands, that internalization of either S. mutans, S. mutans isogenic mutants, or purified ligands is not necessary to trigger cells to release IL-8. We also showed that, besides the implication of monocytes in pulpal inflammation, fibroblast-like cells such as DP and PDL cells are also actively implicated in local inflammation and in the generation of a Th1 response after stimulation with S. mutans cells or antigens

Upregulation of Intercellular Adhesion Molecule 1 and Proinflammatory Cytokines by the Major Surface Proteins of Treponema maltophilum and Treponema lecithinolyticum , the Phylogenetic Group IV Oral Spirochetes Associated with Periodontitis and Endodontic Infections

“…However, with the exception of their LPS or LPS-like materials, none of them has been analyzed at the molecular level. In addition, there are only limited data on induction of IL-8 expression in PDL cells as a result of bacterial factors (12,17), although IL-1␤ is known to be a stimulus for IL-8 expression in PDL cells (1,26). In the present study, we showed that the surface proteins of oral spirochetes cause IL-8 expression in PDL cells.…”

Functions of Cell Surface-Anchored Antigen I/II Family and Hsa Polypeptides in Interactions of Streptococcus gordonii with Host Receptors

“…Since Hsa and AgI/II polypeptides have been shown to interact with receptors on erythrocytes and monocytes (13,53), we investigated the effects of inactivating Hsa or AgI/II polypeptide genes on adhesion of S. gordonii to HEp-2 human epithelial cells. At a multiplicity of infection of 100:1 (ratio of streptococci to HEp-2 cells) about 27% of the input wild-type DL1 bacteria adhered to the epithelial cell monolayers (Fig.…”

The Collagen-Binding Protein Cnm Is Required for Streptococcus mutans Adherence to and Intracellular Invasion of Human Coronary Artery Endothelial Cells

“…Fibronectin, collagen, laminin, and elastin are considered the most common components of ECM (63) and can serve as receptors for bacteria during infection. Some S. mutans surface structures, such as the P1 protein (also known as antigen I/II or SpaP), the wall-anchored protein A (WapA), the biofilm regulatory protein A (BrpA), the autolysin AtlA, the glucosyltransferases (GtfB, GtfC, and GtfD), and the serotype-specific RGP, have been implicated in the pathogenesis of IE by promoting adherence to endothelial tissues and triggering inflammatory responses (17,55,61). More recently, a new surface protein with collagen-and laminin-binding activity, Cnm, which has an uneven distribution among the different serotypes of S. mutans, was identified (47,51,52).…”

“…In some cases, binding to the extracellular matrix (ECM) is the first step in the invasion of host cells (17,58). The ECM is a macromolecular structure that becomes exposed when tissue integrity is damaged by lesions or traumas (63).…”