Enzymatic treatment transforms trypomastigotes of Trypanosoma cruzi into activators of alternative complement pathway and potentiates their uptake by macrophages.
In the absence of bound antibody, trypomastigote bloodstream forms of Trypanosoma cruzi fail to activate the alternative complement pathway. We now demonstrate that treatment with trypsin and, to a lesser extent, with sialidase converts these protozoa into activators of the pathway, as judged by their lysis in normal sera or sera genetically deficient in fourth or second component of complement (C4 or C2) and their Mg2+-dependent consumption of C3 as measured by crossed immunoelectrophoresis. In addition, after pretreatment with enzyme and incubation in C5-deficient serum, trypomastigotes were shown to possess both C3 and properdin factor B (B) on their surface as judged by immunofluorescence. Requirement for the late components C5-C9 was suggested by the failure of C5-deficient sera to lyse trypsin-treated parasites. The inability to activate the alternative complement pathway was regained by these organisms after incubation in vitro. This restoration of insusceptibility was inhibited when puromycin was included in the culture medium. Treatment of the trypomastigotes with trypsin also potentiated their uptake by mouse peritoneal macrophages without apparent interference with their capacity to differentiate and multiply inside the cell. These findings suggest that untreated trypomastigotes normally escape recognition by the alternative pathway in vivo because of the presence on their surface of trypsin- and sialidase-sensitive regulatory molecules, the expression of which is dependent on protein synthesis.
D000818:Animals; D003167:Complement Activation; D003180:Complement C3b Inactivator Proteins / Q000494:pharmacology; D011415:Complement Factor B; D017242:Complement Factor H; D003169:Complement Inactivator Proteins / Q000494:pharmacology; D003170:Complement Pathway, Alternative; D006168:Guinea Pigs; D006801:Humans; D008264:Macrophages / Q000276:immunology*; D008274:Magnesium / Q000494:pharmacology; D051379:Mice; D009439:Neuraminidase / Q000494:pharmacology*; D010587:Phagocytosis; D051381:Rats; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000276:immunology*; D014357:Trypsin / Q000494:pharmacology*
C493495:CFH protein, human; D003180:Complement C3b Inactivator Proteins; D003169:Complement Inactivator Proteins; D017242:Complement Factor H; D009439:Neuraminidase; D014357:Trypsin; D011415:Complement Factor B; D008274:Magnesium