Participation of complement in host defense against capsule-deficient Haemophilus influenzae.

To investigate the role of complement in immunity to capsule-deficient Haemophilus influenzae, rats were depleted of C3 with cobra venom factor and challenged with three different strains of capsule-deficient H. influenzae. Two of them (Rd and U1) did not elaborate type b capsular antigen, whereas the other (S2) elaborated 0.16% of the amount made by its type b parent strain. Depletion of C3 significantly enhanced early intravascular bacterial survival after intravenous inoculation and strikingly increased the susceptibility of rats to infection with capsule-deficient H. influenzae. After intraperitoneal inoculation with strain Rd or U1, C3-depleted rats developed bacteremia, whereas control rats did not; challenge with strain S2 resulted in transient bacteremia in normal rats and in death in C3-depleted animals. To determine whether the greater virulence of strain S2, as compared with strain Rd or U1, was accounted for by the small amounts of capsular antigen it elaborated, we also compared its relative virulence to that of three genetically closely related capsule-deficient variants elaborating either small amounts of type b capsule or producing no detectable b antigen. No difference in virulence was observed among these four variants; all C3-depleted rats inoculated developed bacteremia of similar magnitude followed by similar mortality rates. These studies demonstrate a significant role for complement in host defense mechanisms against capsule-deficient H. influenzae and suggest that interstrain differences of virulence are not attributable to residual elaboration of small amounts of type b capsule.