A role for C5 and C5a-ase in the acute neutrophil response to group B streptococcal infections

Abstract

Congenic C5-deficient and C5-sufficient mice were infected with group B streptococci (GBS) to determine if the polymorphonuclear leukocyte (PMNL) chemoattractant C5a contributes to PMNL recruitment in GBS infection and if GBS C5a-ase reduces C5a-induced PMNL recruitment in vivo. PMNL accumulation was greater in the peritoneum and air spaces of C5-sufficient mice than in CS-deficient mice. Administration of human C5 to C5-deficient mice caused a significant increase in PMNL recruitment following infection with C5a-ase- negative GBS. GBS C5a-ase did not reduce PMNL accumulation in C5-sufficient mice but reduced PMNL recruitment in CS-deficient mice reconstituted with human C5. These data indicate that C5a is important for rapid PMNL recruitment to sites of GBS infection and that GBS C5a-ase inactivates human, but not murine, C5a in vivo. Reduction of the acute inflammatory response by C5a-ase likely contributes to GBS virulence in human neonates.