Role of complement in Mycobacterium avium pathogenesis: In vivo and in vitro analyses of the host response to infection in the absence of complement component C3

We investigated the importance of the host complement system in the pathoge nesis of disease mediated by the intramacrophage pathogen Mycobacterium avi um. Mycobacteria opsonized with complement are efficiently ingested by macr ophages through various complement receptors. Furthermore, unlike other bac teria, mycobacteria can activate both the alternative and classical complem ent pathways in the absence of specific antibodies. Therefore, to examine t he role of complement in the mycobacterial infection process in vivo, mice deficient in complement component C3 were infected with M. avium. Surprisin gly, C3-deficient mice infected intravenously with M. avium displayed no di fference in bacterial burden or granulomatous response compared to wild-typ e control mice. C3-sufficient mice and C3-deficient mice were equally susce ptible to infection by M. avium regardless of the genotype at the bcg locus , a locus known to confer susceptibility to infection with intracellular pa thogens. In vitro studies using mouse bone marrow-derived macrophages resul ted in significant H. avium invasion of macrophages in the absence of C3; h owever, the kinetics of infection were delayed compared to complement-media ted invasion. The data indicate that complement does not play an essential role in mediating Al. avium infections in the mouse and suggest either that other invasion mechanisms can compensate for the absence of complement-med iated entry or that complement is not a major mycobacterial opsonin in vivo .