Proinflammatory activity of glycosylphosphatidylinositol anchors derived from Trypanosoma cruzi: structural and functional analyses.
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.
Almeida
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IC
Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil. ialmeida@icb.usp.br
Gazzinelli
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RT
D000818:Animals; D002240:Carbohydrate Sequence; D014355:Chagas Disease / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D029721:Drosophila Proteins; D017261:Glycosylphosphatidylinositols / Q000737:chemistry* / Q000502:physiology*; D007249:Inflammation / Q000276:immunology; D008070:Lipopolysaccharides / Q000737:chemistry; D008264:Macrophages / Q000276:immunology; D008562:Membrane Glycoproteins / Q000378:metabolism; D008969:Molecular Sequence Data; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014349:Trypanosoma cruzi / Q000472:pathogenicity*
D016207:Cytokines; D029721:Drosophila Proteins; D017261:Glycosylphosphatidylinositols; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors