Role of Complement inMycobacterium aviumPathogenesis: In Vivo and In Vitro Analyses of the Host Response to Infection in the Absence of Complement Component C3

Abstract
We investigated the importance of the host complement system in the pathogenesis of disease mediated by the intramacrophage pathogenMycobacterium avium. Mycobacteria opsonized with complement are efficiently ingested by macrophages through various complement receptors. Furthermore, unlike other bacteria, mycobacteria can activate both the alternative and classical complement pathways in the absence of specific antibodies. Therefore, to examine the role of complement in the mycobacterial infection process in vivo, mice deficient in complement component C3 were infected withM. avium.Surprisingly, C3-deficient mice infected intravenously withM. aviumdisplayed no difference in bacterial burden or granulomatous response compared to wild-type control mice. C3-sufficient mice and C3-deficient mice were equally susceptible to infection byM. aviumregardless of the genotype at thebcglocus, a locus known to confer susceptibility to infection with intracellular pathogens. In vitro studies using mouse bone marrow-derived macrophages resulted in significantM. aviuminvasion of macrophages in the absence of C3; however, the kinetics of infection were delayed compared to complement-mediated invasion. The data indicate that complement does not play an essential role in mediatingM. aviuminfections in the mouse and suggest either that other invasion mechanisms can compensate for the absence of complement-mediated entry or that complement is not a major mycobacterial opsonin in vivo.