title: Insertional inactivation of pac and rmlB genes reduces the release of tumor necrosis factor alpha, interleukin-6, and interleukin-8 induced by Streptococcus mutans in 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.
authors.affiliation: INSERM U 392, Université Louis Pasteur de Strasbourg, F-67400 Illkirch, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Engels-Deutsch
authors.forename: Annelise
authors.initials: A
authors.lastname: Pini
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Yamashita
authors.forename: Yukie
authors.initials: Y
authors.lastname: Shibata
authors.forename: Youssef
authors.initials: Y
authors.lastname: Haikel
authors.forename: Marie
authors.initials: M
authors.lastname: Schöller-Guinard
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Klein
mesh_terms: D018829:Adhesins, Bacterial / Q000276:immunology; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D003731:Dental Caries / Q000276:immunology / Q000382:microbiology; D003782:Dental Pulp / Q000276:immunology / Q000382:microbiology; D005798:Genes, Bacterial; D006801:Humans; D006836:Hydro-Lyases / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis*; D016209:Interleukin-8 / Q000096:biosynthesis*; D008562:Membrane Glycoproteins; D009000:Monocytes / Q000276:immunology / Q000382:microbiology; D016254:Mutagenesis, Insertional; D010513:Periodontal Ligament / Q000276:immunology / Q000382:microbiology; D013290:Streptococcal Infections / Q000276:immunology / Q000382:microbiology; D013295:Streptococcus mutans / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D015850:Interleukin-6; D016209:Interleukin-8; D008562:Membrane Glycoproteins; C055764:S-layer proteins; D014409:Tumor Necrosis Factor-alpha; D006836:Hydro-Lyases; C022771:dTDPglucose 4,6-dehydratase