The major outer sheath protein of Treponema denticola inhibits the binding step of collagen phagocytosis in fibroblasts

Abstract

SummaryBacterial infections contribute to the chronicity of connective tissue lesions in part by perturbing extracellular matrix remodelling processes. We examined a novel mechanism by which the major outer sheath protein (Msp) of the spirochaete Treponema denticola

Modulation of Human Neutrophil Functions In Vitro by Treponema denticola Major Outer Sheath Protein

“…This finding is consistent with studies of Msp-treated fibroblasts (15,27) and T. denticola-treated KB epithelial cells (6), target cells that undergo gross cytoskeletal reorganization but remain viable. Enriched Msp is also known to depolarize HeLa cell membranes, presumably by establishing short-lived ion channels (13).…”

“…Yet there is little knowledge of the T. denticola factors that may modulate key antimicrobial pathways and mechanisms in PMNs. The crucial role of the cytoskeleton in migration and endocytosis, combined with previous findings that the major outer sheath protein (Msp) of T. denticola perturbed actin assembly in fibroblasts (1,15,27), suggested that Msp may modulate human neutrophil chemotaxis and phagocytosis.…”

“…1). The chemotaxis experiments were repeated using the highest concentration of Msp (64 g/ml) which had been heated at 60°C for 30 min or which had been incubated with anti-Msp antibodies or preimmune serum for 1 h at 4°C, followed by absorption by protein A-Sepharose beads (15,27). Both heating and absorption with anti-Msp antibodies reversed the inhibitory effect (Fig.…”

“…Inhibition of actin monomer incorporation into filaments would be expected to impair pseudopod formation. Alternatively, Msp could have affected receptor-mediated immunoglobulin engagement analogously to its reduction of the anticipated affinity modulation when the ␤ 1 integrins of fibroblasts engage collagen (15). Msp pretreatment did not affect the agonist-stimulated oxidative response.…”

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

“…The 53-kDa major surface protein (Msp) of T. denticola ATCC 35405 has been shown to have pore-forming and adhesion activities (13,30). This protein also inhibits agonist-induced Ca 2ϩ release from the internal stores by uncoupling the storeoperated channels (52) and the binding step of collagen phagocytosis in gingival fibroblasts (3). Dentilisin having chymotrypsin-like activity has been found to be located in the outer membrane (10).…”