title: Streptococcus suis capsular polysaccharide inhibits phagocytosis through destabilization of lipid microdomains and prevents lactosylceramide-dependent recognition.
abstract: Streptococcus suis type 2 is a major swine pathogen and a zoonotic agent, causing meningitis in both swine and humans. S. suis infects the host through the respiratory route, reaches the bloodstream, and persists until breaching into the central nervous system. The capsular polysaccharide (CPS) of S. suis type 2 is considered a key virulence factor of the bacteria. Though CPS allows S. suis to adhere to the membrane of cells of the immune system, it provides protection against phagocytosis. In fact, nonencapsulated mutants are easily internalized and killed by macrophages and dendritic cells. The objective of this work was to study the molecular mechanisms by which the CPS of S. suis prevents phagocytosis. By using latex beads covalently linked with purified CPS, it was shown that CPS itself was sufficient to inhibit entry of both latex beads and bystander fluorescent beads into macrophages. Upon contact with macrophages, encapsulated S. suis was shown to destabilize lipid microdomains at the cell surface, to block nitric oxide (NO) production during infection, and to prevent lactosylceramide accumulation at the phagocytic cup during infection. In contrast, the nonencapsulated mutant was easily internalized via lipid rafts, in a filipin-sensitive manner, leading to lactosylceramide recruitment and strong NO production. This is the first report to identify a role for CPS in lipid microdomain stability and to recognize an interaction between S. suis and lactosylceramide in phagocytes.
authors: Groupe de Recherche sur les Maladies Infectieuses du Porc and Centre de Recherche en Infectiologie Porcine, Faculté de Médecine Vétérinaire, Université de Montréal, Montreal, Quebec, Canada.
authors: Mathieu
authors: M
authors: Houde
authors: Marcelo
authors: M
authors: Gottschalk
authors: Fleur
authors: F
authors: Gagnon
authors: Marie-Rose
authors: MR
authors: Van Calsteren
authors: Mariela
authors: M
authors: Segura
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism*; D001422:Bacterial Adhesion; D002236:Carbohydrate Conformation; D002478:Cells, Cultured; D005260:Female; D005372:Filipin / Q000494:pharmacology; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D007790:Lactosylceramides / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000502:physiology; D021962:Membrane Microdomains / Q000187:drug effects*; D051379:Mice; D008863:Microspheres; D010587:Phagocytosis / Q000187:drug effects*; D011135:Polysaccharides, Bacterial / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D017011:Streptococcus suis / Q000187:drug effects / Q000378:metabolism* / Q000472:pathogenicity; D014774:Virulence
chemical_list: D000900:Anti-Bacterial Agents; D015703:Antigens, CD; D007790:Lactosylceramides; D011135:Polysaccharides, Bacterial; C009744:CDw17 antigen; D005372:Filipin