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Alternative activation and increase of Trypanosoma cruzi survival in murine macrophages stimulated by cruzipain, a parasite antigen
Author(s) -
Stempin Cinthia,
Giordanengo Laura,
Gea Susana,
Cerbán Fabio
Publication year - 2002
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.72.4.727
Subject(s) - trypanosoma cruzi , biology , arginase , antigen , lipopolysaccharide , spleen , immune system , intracellular , microbiology and biotechnology , macrophage , in vitro , immunology , parasite hosting , arginine , biochemistry , amino acid , world wide web , computer science
We studied the macrophage (Mo) activation pathways through Mo interaction with immunogenic Trypanosoma cruzi antigens as cruzipain (Cz) and R13. J774 cells, peritoneal and spleen Mo from normal mice, were used. Although Mo classic activation was observed in the presence of lipopolysaccharide, evaluated through nitric oxide (NO) and interleukin (IL)‐12 production, Cz and R13 did not activate Mo in this way. To study the alternative pathway, we examined the arginase activity in Mo cultured with Cz. An increase of arginase activity was detected in all Mo sources assayed. An increase of IL‐10 and transforming growth factor‐β in culture supernatants from Mo stimulated with Cz was observed. The study of expression of B7.1 and B7.2 in spleen Mo revealed that Cz induces preferential expression of B7.2. In vitro studies revealed that Cz stimulated J774 cells and then, infected with trypomastigotes of T. cruzi , developed a higher number of intracellular parasites than unstimulated infected Mo. Thus, Cz favors the perpetuation of T. cruzi infection. In addition, a down‐regulation of inducible NO synthase was observed in J774 cells stimulated with Cz. These results suggest that Cz interaction with Mo could modulate the immune response generated against T. cruzi through the induction of a preferential metabolic pathway in Mo.