Role of the alternative and classical complement activation pathway in complement mediated killing against...

There is considerable evidence that phase variation among transparent and opaque colony phenotypes of Streptococcus pneumoniae (Spn) plays an important role in the pneumococcal adherence and invasion. The current study was designed to investigate the interactions of the opacity phenotype variants of Spn with specific complement pathway activation in a mouse model of acute otitis media (AOM). Although the opaque colony phenotype was expected to be more resistant to complement mediated killing compared to the transparent Spn variant, we discovered that C3b deposition on the transparent Spn is, in large part, dependent on the alternative pathway activation. There were no significant differences in resistance to complement mediated opsonophagocytosis between the two variants in factor B deficient mice. In addition, an in vitro study demonstrated that significantly more C4b-binding protein (C4BP) (the classical pathway inhibitor) and factor H (FH) (the alternative pathway inhibitor) bound to the transparent strain compared with the opaque one. Our data suggest that the difference in the relative virulence of Spn opacity phenotypes is associated with its ability to evade complement-mediated opsonophagocytosis in a mouse model of pneumococcal AOM.