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(Journal of Leukocyte Biology. 2001;70:467-477.)
© 2001 by Society for Leukocyte Biology

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

Igor C. Almeida^* and Ricardo T. Gazzinelli

^* Department of Parasitology, University of São Paulo, São Paulo, SP, Brazil; and
Department of Biochemistry and Immunology, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil

Correspondence: Dr. Igor C. Almeida, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 1374, São Paulo, SP 05508-900, Brazil. E-mail: ialmeida{at}icb.usp.br

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 activation of innate immunity. Recent studies have shown the stimulatory activity of protozoan-derived glycosylphosphatidylinositol (GPI) anchors on cultured macrophages. In this review, we provide 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 characterized signaling pathways triggered by T. cruzi-derived GPI anchors, which lead to the synthesis of proinflammatory cytokines in macrophages. Finally, we discuss the implications of these findings in resistance and pathogenesis during the infection with T. cruzi.

Key Words: protozoan parasites • macrophages • innate immunity • cytokine • Toll-like receptors

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