PMID- 17307800 OWN - NLM STAT- MEDLINE DCOM- 20070827 LR - 20181211 IS - 0953-8178 (Print) IS - 0953-8178 (Linking) VI - 19 IP - 4 DP - 2007 Apr TI - TLR2-dependent recognition of Streptococcus suis is modulated by the presence of capsular polysaccharide which modifies macrophage responsiveness. PG - 375-89 AB - Streptococcus suis capsular type 2 is an important swine pathogen and an agent of zoonosis. Although meningitis is the most common form of disease, septicemia and septic shock are also frequently reported. Despite reports that CD14 is involved in the recognition of encapsulated S. suis by host cells, the mechanisms underlying exacerbated release of pro-inflammatory cytokines, which may have a negative impact on disease outcome, are unclear. Here, we demonstrated that stimulation of human monocytes by whole encapsulated S. suis or its purified cell wall components influences the relative expression of Toll-like receptor (TLR)-2 and CD14 mRNA. Moreover, this stimulation triggered the release of cytokines (tumor necrosis factor-alpha, IL-1beta and IL-6) and chemokines (IL-8 and monocyte chemoattractant protein-1), which was significantly reduced by antibody-mediated blocking of TLR2 but not TLR4. Mouse macrophages deficient in TLR2 also showed impaired cytokine responses to encapsulated bacteria. Given that this response was completely abrogated in myeloid differentiation factor 88 (MyD88)-deficient macrophages, other TLRs might also be involved. Furthermore, we demonstrated that the presence of capsular polysaccharide (CPS)-modulated S. suis interactions with TLRs. In the absence of CPS, uncovered cell wall components induced cytokine and chemokine production via TLR2-dependent as well as -independent pathways, whereas CPS contributes to MCP-1 production in a MyD88-independent manner. Overall, this study contributes to a better understanding of the inflammatory processes induced by an encapsulated pathogen and suggests that the relative expression of CPS, known to be modulated during bacterial invasion and dissemination in the host, might alter interactions with host cells and, consequently, the outcome of the inflammatory response. FAU - Graveline, Richard AU - Graveline R AD - Groupe de Recherche sur les Maladies Infectieuses du Porc and Centre de Recherche en Infectiologie Porcine, Faculte de Medecine Veterinaire, Universite de Montreal, 3200 rue Sicotte, St-Hyacinthe, Quebec, J2S 2M2, Canada. FAU - Segura, Mariela AU - Segura M FAU - Radzioch, Danuta AU - Radzioch D FAU - Gottschalk, Marcelo AU - Gottschalk M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070216 PL - England TA - Int Immunol JT - International immunology JID - 8916182 RN - 0 (Antibodies, Monoclonal) RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Interleukins) RN - 0 (Lipopeptides) RN - 0 (Lipopolysaccharide Receptors) RN - 0 (Myd88 protein, mouse) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (Oligopeptides) RN - 0 (Polysaccharides, Bacterial) RN - 0 (RNA, Messenger) RN - 0 (TLR2 protein, human) RN - 0 (TLR4 protein, human) RN - 0 (Tlr2 protein, mouse) RN - 0 (Toll-Like Receptor 2) RN - 0 (Toll-Like Receptor 4) RN - 0 (Tumor Necrosis Factor-alpha) RN - DZX5IUA94D (macrophage stimulatory lipopeptide 2) SB - IM MH - Animals MH - Antibodies, Monoclonal/pharmacology MH - Cell Line MH - Cell Line, Tumor MH - Cell Wall/immunology MH - Chemokine CCL2/metabolism MH - Gene Expression/drug effects MH - Humans MH - Immunity, Innate/drug effects/*immunology MH - Interleukins/metabolism MH - Lipopeptides MH - Lipopolysaccharide Receptors/genetics/metabolism MH - Macrophages/drug effects/*immunology/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Myeloid Differentiation Factor 88/genetics MH - Oligopeptides/pharmacology MH - Polysaccharides, Bacterial/*immunology/pharmacology MH - RNA, Messenger/genetics/metabolism MH - Streptococcus suis/*immunology MH - Toll-Like Receptor 2/antagonists & inhibitors/genetics/*metabolism MH - Toll-Like Receptor 4/antagonists & inhibitors/genetics/metabolism MH - Tumor Necrosis Factor-alpha/metabolism EDAT- 2007/02/20 09:00 MHDA- 2007/08/28 09:00 CRDT- 2007/02/20 09:00 PHST- 2007/02/20 09:00 [pubmed] PHST- 2007/08/28 09:00 [medline] PHST- 2007/02/20 09:00 [entrez] AID - dxm003 [pii] AID - 10.1093/intimm/dxm003 [doi] PST - ppublish SO - Int Immunol. 2007 Apr;19(4):375-89. doi: 10.1093/intimm/dxm003. Epub 2007 Feb 16.