title: Implication of TLR- but not of NOD2-signaling pathways in dendritic cell activation by group B Streptococcus serotypes III and V.
abstract: Group B Streptococcus (GBS) is an important agent of life-threatening invasive infection. It has been previously shown that encapsulated type III GBS is easily internalized by dendritic cells (DCs), and that this internalization had an impact on cytokine production. The receptors underlying these processes are poorly characterized. Knowledge on the mechanisms used by type V GBS to activate DCs is minimal. In this work, we investigated the role of Toll-like receptor (TLR)/MyD88 signaling pathway, the particular involvement of TLR2, and that of the intracellular sensing receptor NOD2 in the activation of DCs by types III and V GBS. The role of capsular polysaccharide (CPS, one of the most important GBS virulence factors) in bacterial-DC interactions was evaluated using non-encapsulated mutants. Despite differences in the role of CPS between types III and V GBS in bacterial internalization and intracellular survival, no major differences were observed in their capacity to modulate release of cytokines by DC. For both serotypes, CPS had a minor role in this response. Production of cytokines by DCs was shown to strongly rely on MyD88-dependent signaling pathways, suggesting that DCs recognize GBS and become activated mostly through TLR signaling. Yet, GBS-infected TLR2-/- DCs only showed a partial reduction in the production of IL-6 and CXCL1 compared to control DCs. Surprisingly, CXCL10 release by type III or type V GBS-infected DCs was MyD88-independent. No differences in DC activation were observed between NOD2-/- and control DCs. These results demonstrate the involvement of various receptors and the complexity of the cytokine production pathways activated by GBS upon DC infection.
authors.affiliation: Laboratory of Immunology, Faculty of Veterinary Medicine, University of Montreal, St-Hyacinthe, Quebec, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Lemire
authors.affiliation: Laboratory of Immunology, Faculty of Veterinary Medicine, University of Montreal, St-Hyacinthe, Quebec, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Roy
authors.affiliation: Public Health Ontario, Toronto, Ontario, Canada; Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Nahuel
authors.initials: N
authors.lastname: Fittipaldi
authors.affiliation: Bacterial and Parasitic Diseases Research Division, National Institute of Animal Health, National Agriculture and Food Research Organization, Tsukuba, Ibaraki, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Okura
authors.affiliation: Bacterial and Parasitic Diseases Research Division, National Institute of Animal Health, National Agriculture and Food Research Organization, Tsukuba, Ibaraki, Japan; The United Graduate School of Veterinary Sciences, Gifu University, Gifu, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Takamatsu
authors.affiliation: Laboratory of Immunology, Faculty of Veterinary Medicine, University of Montreal, St-Hyacinthe, Quebec, Canada.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Bergman
authors.affiliation: Laboratory of Immunology, Faculty of Veterinary Medicine, University of Montreal, St-Hyacinthe, Quebec, Canada.
authors.forename: Mariela
authors.initials: M
authors.lastname: Segura
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000382:microbiology*; D005260:Female; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology*; D053473:Nod2 Signaling Adaptor Protein / Q000276:immunology*; D015398:Signal Transduction; D013290:Streptococcal Infections / Q000276:immunology*; D013292:Streptococcus agalactiae / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000276:immunology*
chemical_list: D053594:Myeloid Differentiation Factor 88; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2