title: Group B Streptococcus and Streptococcus suis capsular polysaccharides induce chemokine production by dendritic cells via Toll-like receptor 2- and MyD88-dependent and -independent pathways.
abstract: Streptococcus agalactiae (also known as group B Streptococcus [GBS]) and Streptococcus suis are encapsulated streptococci causing severe septicemia and meningitis. Bacterial capsular polysaccharides (CPSs) are poorly immunogenic, but anti-CPS antibodies are essential to the host defense against encapsulated bacteria. The mechanisms underlying anti-CPS antibody responses are not fully elucidated, but the biochemistry of CPSs, particularly the presence of sialic acid, may have an immunosuppressive effect. We investigated the ability of highly purified S. suis and GBS native (sialylated) CPSs to activate dendritic cells (DCs), which are crucial actors in the initiation of humoral immunity. The influence of CPS biochemistry was studied using CPSs extracted from different serotypes within these two streptococcal species, as well as desialylated CPSs. No interleukin-1β (IL-1β), IL-6, IL-12p70, tumor necrosis factor alpha (TNF-α), or IL-10 production was observed in S. suis or GBS CPS-stimulated DCs. Moreover, these CPSs exerted immunosuppressive effects on DC activation, as a diminution of gamma interferon (IFN-γ)-induced B cell-activating factor of the tumor necrosis factor family (BAFF) expression was observed in CPS-pretreated cells. However, S. suis and GBS CPSs induced significant production of CCL3, via partially Toll-like receptor 2 (TLR2)- and myeloid differentiation factor 88 (MyD88)-dependent pathways, and CCL2, via TLR-independent mechanisms. No major influence of CPS biochemistry was observed on the capacity to induce chemokine production by DCs, indicating that DCs respond to these CPSs in a patterned way rather than a structure-dedicated manner.
authors.affiliation: Laboratory of Immunology, Faculty of Veterinary Medicine, University of Montreal, Saint-Hyacinthe, Quebec, Canada.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Calzas
authors.forename: Guillaume
authors.initials: G
authors.lastname: Goyette-Desjardins
authors.forename: Paul
authors.initials: P
authors.lastname: Lemire
authors.forename: Fleur
authors.initials: F
authors.lastname: Gagnon
authors.forename: Claude
authors.initials: C
authors.lastname: Lachance
authors.forename: Marie-Rose
authors.initials: MR
authors.lastname: Van Calsteren
authors.forename: Mariela
authors.initials: M
authors.lastname: Segura
mesh_terms: D000818:Animals; D053264:B-Cell Activating Factor / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D054405:Chemokine CCL3 / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D056724:Immunity, Humoral / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007378:Interleukins / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology* / Q000378:metabolism; D011135:Polysaccharides, Bacterial / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013290:Streptococcal Infections / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D013292:Streptococcus agalactiae / Q000276:immunology* / Q000378:metabolism; D017011:Streptococcus suis / Q000276:immunology* / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D053264:B-Cell Activating Factor; C496534:Ccl3 protein, mouse; D054405:Chemokine CCL3; D007378:Interleukins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011135:Polysaccharides, Bacterial; C493486:Tlr2 protein, mouse; C505720:Tnfsf13b protein, mouse; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma