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 activate the alternative pathway of human complement was examined. Incubation of L. monocytogenes with human serum in optimal conditions (20% Mg2+EGTA [ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid]-chelated serum) consumed (31.3 +/- 3.9)% of C3 hemolytic activity and led to similar amounts of C3 deposition among the 27 strains tested, except for a rough mutant and the penicillin-induced L forms 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 provided that L. monocytogenes induces the deposition of C3b and its cleavage products iC3b and C3d through ester and amide linkages, as demonstrated by the analysis of the released products of radiolabelled purified C3 after treatment with hydroxylamine. Our results clearly demonstrate that L. monocytogenes activates the alternative pathway of human complement, suggesting that bacteria in the blood or in tissues of infected patients are opsonized and targeted to C3 receptor-bearing cells such as macrophages.
Croize
J
J
Laboratoire d'immunochimie, DBMS/ICH, Institut National de la Santé et de la Recherche Médicale U. 238, Grenoble, France.
Arvieux
J
J
Berche
P
P
Colomb
M G
MG
D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D003176:Complement C3 / Q000737:chemistry / Q000378:metabolism*; D003170:Complement Pathway, Alternative; D006801:Humans; D066298:In Vitro Techniques; D008089:Listeria monocytogenes / Q000276:immunology* / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D013045:Species Specificity
D003176:Complement C3; D010446:Peptide Fragments