The Role of Complement in Host Defense Against Bacteremia

Abstract

Abstract In order to further study the role of complement in host defense, a model of pneumococcal bacteremia was developed in guinea pigs and mice. Type 4 pneumococci grown overnight in trypticase soy broth were injected intravenously, and clearance rates and organ distribution were studied by colony counts and 59Fe labeling of bacteria. C4-deficient (C4D) and normal NIH guinea pigs (GP) had similar patterns of rapid clearance. This was associated with activation of approximately 20,000 C3 molecules per bacterium. However, cobra venom factor- (CVF)treated animals had significantly delayed clearance of bacteria which was followed by overwhelming sepsis and death. Immunization produced enhanced clearance in normal GP but not in C4D animals, suggesting the requirement for an intact classical complement pathway for efficient immune clearance. Actively immunized CVF animals continued to exhibit delayed clearance and subsequent death. Sequestration of bacteria occurred in the liver, spleen, and lung in the normal animal.