ACTIVATION OF THE HUMAN-COMPLEMENT ALTERNATIVE PATHWAY BY LISTERIA-MONOCYTOGENES - EVIDENCE FOR DIRECT BINDING AND PROTEOLYSIS OF THE C3 COMPONENT ON BACTERIA

The capacity of the intracellular pathogen Listeria monocytogenes to a ctivate the alternative pathway of human complement was examined. Incu bation of L. monocytogenes with human serum in optimal conditions (20% Mg(2+)EGTA [ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetr aacetic acid]-chelated serum) consumed (31.3 +/- 3.9)% of C3 hemolytic activity and led to similar amounts of C3 deposition among the 27 str ains tested, except for a rough mutant and the penicillin-induced L fo rms of strain EGD, which bound reduced amounts of C3. The same results were obtained with strains belonging to related species (L. innocua, L. seeligeri, L. welshimeri, and L. ivanovii). Direct evidence is prov ided that L. monocytogenes induces the deposition of C3b and its cleav age products iC3b and C3d through ester and amide linkages, as demonst rated by the analysis of the released products of radiolabelled purifi ed C3 after treatment with hydroxylamine. Our results clearly demonstr ate that L. monocytogenes activates the alternative pathway of human c omplement, suggesting that bacteria in the blood or in tissues of infe cted patients are opsonized and targeted to C3 receptor-bearing cells such as macrophages.