title: Role of capsule and suilysin in mucosal infection of complement-deficient mice with Streptococcus suis.
abstract: Virulent Streptococcus suis serotype 2 strains are invasive extracellular bacteria causing septicemia and meningitis in piglets and humans. One objective of this study was to elucidate the function of complement in innate immune defense against S. suis. Experimental infection of wild-type (WT) and C3(-/-) mice demonstrated for the first time that the complement system protects naive mice against invasive mucosal S. suis infection. S. suis WT but not an unencapsulated mutant caused mortality associated with meningitis and other pathologies in C3(-/-) mice. The capsule contributed also substantially to colonization of the upper respiratory tract. Experimental infection of C3(-/-) mice with a suilysin mutant indicated that suilysin expression facilitated an early disease onset and the pathogenesis of meningitis. Flow cytometric analysis revealed C3 antigen deposition on the surface of ca. 40% of S. suis WT bacteria after opsonization with naive WT mouse serum, although to a significantly lower intensity than on the unencapsulated mutant. Ex vivo multiplication in murine WT and C3(-/-) blood depended on capsule but not suilysin expression. Interestingly, S. suis invasion of inner organs was also detectable in C5aR(-/-) mice, suggesting that chemotaxis and activation of immune cells via the anaphylatoxin receptor C5aR is, in addition to opsonization, a further important function of the complement system in defense against mucosal S. suis infection. In conclusion, we unequivocally demonstrate here the importance of complement against mucosal S. suis serotype 2 infection and that the capsule of this pathogen is also involved in escape from complement-independent immunity.
authors.affiliation: Institute for Microbiology, University of Veterinary Medicine Hanover, Hanover, Germany.
authors.forename: Maren
authors.initials: M
authors.lastname: Seitz
authors.forename: Andreas
authors.initials: A
authors.lastname: Beineke
authors.forename: Alena
authors.initials: A
authors.lastname: Singpiel
authors.forename: Jörg
authors.initials: J
authors.lastname: Willenborg
authors.forename: Pavel
authors.initials: P
authors.lastname: Dutow
authors.forename: Ralph
authors.initials: R
authors.lastname: Goethe
authors.forename: Peter
authors.initials: P
authors.lastname: Valentin-Weigand
authors.forename: Andreas
authors.initials: A
authors.lastname: Klos
authors.forename: Christoph G
authors.initials: CG
authors.lastname: Baums
mesh_terms: D000706:Anaphylatoxins / Q000502:physiology; D000818:Animals; D016667:Bacterial Capsules / Q000502:physiology*; D003165:Complement System Proteins / Q000502:physiology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006460:Hemolysin Proteins / Q000502:physiology*; D054884:Host-Pathogen Interactions / Q000502:physiology; D007113:Immunity, Innate / Q000502:physiology; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009296:Nasal Cavity / Q000382:microbiology; D013290:Streptococcal Infections / Q000382:microbiology / Q000401:mortality; D017011:Streptococcus suis / Q000472:pathogenicity / Q000502:physiology*; D014774:Virulence
chemical_list: D000706:Anaphylatoxins; D006460:Hemolysin Proteins; C104760:suilysin; D003165:Complement System Proteins