Evasion of alternative complement pathway by Trypanosoma cruzi results from inefficient binding of factor B.
During its differentiation in the insect vector to a stage infective for the mammalian host, Trypanosoma cruzi becomes resistant to lysis by the alternative pathway of complement. To elucidate the mechanism of complement evasion, we studied control of complement activation on the surface of the noninfective epimastigote and the infective culture-derived metacyclic trypomastigote stages (CMT) of T. cruzi. It was found that the predominant form of complement component C3 on epimastigotes is C3b, whereas the majority of C3 on CMT is in the form of the hemolytically inactive fragment iC3b, which cannot participate in C5 convertase formation or lead to deposition of the lytic C5b-9 complex. Our results also showed that C3 binds by a covalent ester linkage to surface molecules of different molecular weight in the epimastigote stage and CMT. Binding studies with purified complement components indicated that CMT do not support efficient formation of an alternative pathway C3 convertase. C3b on the parasite surface fails to bind the amplification component, factor B, rather than showing enhanced binding of the control component, factor H. These results identify the biochemical basis for evasion of complement-mediated killing in T. cruzi and reveal a mechanism for developmental regulation of complement activation.
D000818:Animals; D002454:Cell Differentiation; D003167:Complement Activation; D003176:Complement C3 / Q000378:metabolism*; D003179:Complement C3b / Q000378:metabolism; D003180:Complement C3b Inactivator Proteins / Q000378:metabolism; D003186:Complement C9 / Q000378:metabolism; D011415:Complement Factor B / Q000378:metabolism*; D011416:Complement Factor D / Q000378:metabolism; D017242:Complement Factor H; D003170:Complement Pathway, Alternative; D004792:Enzyme Precursors / Q000378:metabolism*; D011951:Receptors, Complement / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000166:cytology / Q000276:immunology*
D003176:Complement C3; D003180:Complement C3b Inactivator Proteins; D003186:Complement C9; D004792:Enzyme Precursors; D011951:Receptors, Complement; D003179:Complement C3b; D017242:Complement Factor H; D011416:Complement Factor D; D011415:Complement Factor B