title: Role of surface proteins SspA and SspB of Streptococcus gordonii in innate immunity.
abstract: Streptococcus gordonii, a normal inhabitant of the human oral cavity, is a potential live vaccine vehicle. Several pathogen-associated molecular patterns from S. gordonii that are recognized by antigen-presenting cells have recently been identified. In this study, we have identified that the cell-wall-anchored proteins SspA and SspB are immunostimulatory components of S. gordonii. SspA and SspB are members of the antigen I/II family of proteins widely expressed by viridans oral streptococci. The results showed that the mutant (OB219) lacking SspA and SspB had a reduced ability to induce cytokine/chemokine production in epithelial cells and bone-marrow-derived dendritic cells as compared with the parent strain (DL1). Purified SspA induced interleukin-6 and monocyte chemotatic protein-1 production from human lung epithelial A549 cells. The induction could be inhibited by a function-blocking anti-β1 integrin mAb and the purified SspA could bind to β1 integrin precoated on microtitre plates, suggesting that the induction was effected by SspA-β1 integrin interactions. The role of SspA and SspB in innate immunity was further demonstrated in a mouse intranasal challenge experiment, which showed that the clearance of OB219, the recruitment of neutrophils (as indicated by myeloperoxidase activity), and chemokine and cytokine production in the lungs of OB219-inoculated mice were delayed or reduced as compared with the DL1-inoculated mice. In addition to the above, S. gordonii OB219 was more sensitive to polymyxin, nisin and histatin-5 than DL1, suggesting that SspA and SspB also play a role in susceptibility to cationic antimicrobial peptides. Collectively, the results indicate that SspA and SspB are immunostimulatory components of S. gordonii and play an important role in modulating the host's innate immunity.
authors.affiliation: Canadian Center for Vaccinology, Dalhousie University and the IWK Health Centre, Halifax, NS, Canada.|Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada.|Department of Applied Oral Sciences, Faculty of Dentistry, Dalhousie University, Halifax, NS, Canada.
authors.forename: Elisoa
authors.initials: E
authors.lastname: Andrian
authors.affiliation: Canadian Center for Vaccinology, Dalhousie University and the IWK Health Centre, Halifax, NS, Canada.|Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada.
authors.forename: Gaofu
authors.initials: G
authors.lastname: Qi
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada.|Canadian Center for Vaccinology, Dalhousie University and the IWK Health Centre, Halifax, NS, Canada.|Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada.|Canadian Center for Vaccinology, Dalhousie University and the IWK Health Centre, Halifax, NS, Canada.|Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Halperin
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada.|Department of Applied Oral Sciences, Faculty of Dentistry, Dalhousie University, Halifax, NS, Canada.|Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada.|Canadian Center for Vaccinology, Dalhousie University and the IWK Health Centre, Halifax, NS, Canada.
authors.forename: Song F
authors.initials: SF
authors.lastname: Lee
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000276:immunology*; D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D051379:Mice; D008807:Mice, Inbred BALB C; D013290:Streptococcal Infections / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D054773:Streptococcus gordonii / Q000235:genetics / Q000276:immunology*
chemical_list: D018829:Adhesins, Bacterial; D016207:Cytokines; C082314:SspA protein, bacteria; C068465:salivary agglutinin receptor, Streptocococcus