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.