title: Immune receptors involved in Streptococcus suis recognition by dendritic cells.
abstract: Streptococcus suis is an important swine pathogen and an emerging zoonotic agent of septicemia and meningitis. Knowledge on host immune responses towards S. suis, and strategies used by this pathogen for subversion of these responses is scarce. The objective of this study was to identify the immune receptors involved in S. suis recognition by dendritic cells (DCs). Production of cytokines and expression of co-stimulatory molecules by DCs were shown to strongly rely on MyD88-dependent signaling pathways, suggesting that DCs recognize S. suis and become activated mostly through Toll-like receptor (TLR) signaling. Supporting this fact, TLR2(-/-) DCs were severely impaired in the release of several cytokines and the surface expression of CD86 and MHC-II. The release of IL-12p70 and CXC10, and the expression of CD40 were found to depend on signaling by both TLR2 and TLR9. The release of IL-23 and CXCL1 were partially dependent on NOD2. Finally, despite the fact that MyD88 signaling was crucial for DC activation and maturation, MyD88-dependent pathways were not implicated in S. suis internalization by DCs. This first study on receptors involved in DC activation by S. suis suggests a major involvement of MyD88 signaling pathways, mainly (but not exclusively) through TLR2. A multimodal recognition involving a combination of different receptors seems essential for DC effective response to S. suis.
authors.affiliation: Department of Pathology and Microbiology, Faculty of Veterinary Medicine, Université de Montréal, St-Hyacinthe, Québec, Canada.
authors.forename: Marie-Pier
authors.initials: MP
authors.lastname: Lecours
authors.forename: Mariela
authors.initials: M
authors.lastname: Segura
authors.forename: Nahuel
authors.initials: N
authors.lastname: Fittipaldi
authors.forename: Serge
authors.initials: S
authors.lastname: Rivest
authors.forename: Marcelo
authors.initials: M
authors.lastname: Gottschalk
mesh_terms: D000818:Animals; D051940:B7-2 Antigen / Q000096:biosynthesis; D019013:CD40 Antigens / Q000378:metabolism; D002469:Cell Separation; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000382:microbiology*; D005434:Flow Cytometry; D005802:Genes, MHC Class II; D005822:Genetic Vectors; D007107:Immune System; D053759:Interleukin-23 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal / Q000379:methods; D008954:Models, Biological; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D053473:Nod2 Signaling Adaptor Protein / Q000378:metabolism; D015398:Signal Transduction; D017011:Streptococcus suis / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D051940:B7-2 Antigen; D019013:CD40 Antigens; D016207:Cytokines; D053759:Interleukin-23; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; C493486:Tlr2 protein, mouse; C495370:Tlr9 protein, mouse; D051195:Toll-Like Receptor 2; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors