ROLE OF COMPLEMENT COMPONENT C1Q IN PHAGOCYTOSIS OF LISTERIA-MONOCYTOGENES BY MURINE MACROPHAGE-LIKE CELL-LINES

Listeria monocytogenes is a facultative intracellular pathogen of a gr eat variety of cells. Among them, macrophages constitute the major eff ector cells of listerial immunity during the course of an infection. A lthough the molecular bases of L. monocytogenes attachment and entry t o phagocytes are not completely understood, it has been demonstrated t hat C3b significantly increases L. monocytogenes uptake by macrophages via complement receptor type 3. The first component of complement, Cl q, is present in organic fluids at a relatively high concentration, an d C1q receptor sites in macrophages are also abundant. In the present report, results of studies on the role of C1q in the internalization a nd infectivity of L. monocytogenes by macrophages are presented. L. mo nocytogenes uptake is enhanced by prior treatment of bacteria with nor mal sera. Heated serum or C1q-deficient serum abrogates this enhanceme nt. Purified Clq specifically restored uptake. This effect was blocked by the addition of F(ab')2 anti-C1q antibody but not by an irrelevant matched antibody. Direct binding of C1q to L. monocytogenes was speci fic, saturable, and dose dependent with both fluorescent and radiolabe led C1q. N-Acetyl-D-alanyl-L-isoglutamine, diaminopimelic acid, and L- rhamnose caused a significant dose-dependent inhibition of C1q binding to bacteria, suggesting that these molecules, at least, are involved in the attachment of C1q to L. monocytogenes cell wall. When C1q bindi ng structures on macrophagelike cells were blocked with saturating con centrations of C1q, the uptake of C1q-opsonized bacteria was less than in untreated cells. These experiments demonstrate that, in addition t o other reported mechanisms, L. monocytogenes binds C1q, which mediate s enhanced uptake by macrophages through Clq binding structures.