Immunological characterization of antigens released by Trypanosoma cruzi-infected cells

Chagas' disease, caused by Trypanosoma cruzi, is characterized by the appea rance of pathological lesions in the heart and other tissues during the chr onic phase. The mechanisms responsible for such damage are still unclear. I n the vertebrate host, T. cruzi replicates intracellularly before transform ing from amastigotes into trypomastigotes. The infected host cell then lyse s, releasing the cytoplasmic contents and the parasites that shed membrane glycoproteins soon after release. The sum of all these components we have t ermed released antigen (Rag). We characterized antigens, released in vitro by fibroblasts infected with T. cruzi, obtained by concentrating conditione d serum-free culture media. The results demonstrate that Rag contains a com plex protein mixture including stage-specific T, cruzi antigens (Ssp-1, -2, -4), glucose-regulated protein (Grp) 78h, and peptides recognized by the m onoclonal antibody 2B10. These peptides exhibit neuraminidase activity and are expressed by intracellular and 10 similar to 20% of released trypomasti gotes. Additionally, Rag is recognized by sera from T. cruzi-infected mice and human chagasic patients. Rag also stimulates in vitro production of int erferon-gamma by splenocytes from resistant C57B1/6 and susceptible BALB/c infected mice and interleukin-4 by splenocytes from BALB/c infected mice. A ltogether these results indicate that Rag is immunologically relevant and c ould contribute to pathogenesis of T. cruzi infection.