Proinflammatory activity of glycosylphosphatidylinositol anchors derived from Trypanosoma cruzi: structural and functional analyses

Abstract: A strong activation of macrophages is observed during acute infection with Trypanosoma cruzi. Little is known, however, about the parasite molecules that are responsible for this early acti-vation of innate immunity. Recent studies have shown the stimulatory activity of protozoan-de-rived glycosylphosphatidylinositol (GPI) anchors on cultured macrophages. In this review, we pro-vide a detailed analysis of the correlation between structure and proinflammatory activity by T. cruzi-derived GPI anchors. We also cover the studies that have identified the Toll-like receptor 2 as a functional GPI receptor and have partially charac-terized signaling pathways triggered by T. cruzi-derived GPI anchors, which lead to the synthesis of proinflammatory cytokines in macrophages. Fi-nally, we discuss the implications of these findings in resistance and pathogenesis during the infection with T. cruzi. J. Leukoc. Biol. 70: 467–477; 2001. Key Words: protozoan parasites z macrophages z innate immunity z cytokine z Toll-like receptor