Host and parasite factors affecting the invasion of mononuclear phagocytes by Trypanosoma cruzi.
Epimastigotes and trypomastigotes of Trypanosoma cruzi enter mouse and human macrophages by phagocytosis. Organisms are initially found in a parasitophorous vacuole, and fusion with lysosomes promptly ensues. Epimastigotes are rapidly killed and digested in phagolysosomes. Trypomastigotes, however, soon escape the confines of the vacuolar system and reach the cytoplasm, where they replicate. Metacyclic trypomastigotes are quickly taken up by mouse and human macrophages. In contrast, blood-form trypomastigotes are resistant to interiorization by mononuclear phagocytes. This effect can be overcome, without affecting parasite survival, by opsonization of the parasites with immunoglobulin G (IgG)-class antibodies or by removal of trypomastigote surface peptides with trypsin. The major surface glycoprotein (relative molecular mass 90 000) of the mammalian stages of T. cruzi has been implicated in this antiphagocytic effect. This surface glycoprotein seems to have glycosidase activity, and the antiphagocytic effect may be mediated via the removal of sugar residues necessary for parasite internalization by macrophages. This enzyme activity may explain other evasion mechanisms displayed by T. cruzi bloodstream forms. These include antibody-mediated complement lysis and Fc-receptor-mediated phagocytosis. Trypomastigotes are, however, promptly killed in mouse and human macrophages activated by either in vivo infection or in vitro treatment with sensitized, antigen-stimulated, T-cell products. Increased production of reactive oxygen intermediates by activated cells has been implicated as the mechanism of intracellular killing in mononuclear phagocytes. Opsonization by IgG-class antibodies enhances uptake of the parasites but does not affect their fate in normal mononuclear phagocytes. In contrast, it enhances their killing by activated macrophages, suggesting that antibodies may have a major protective role only in the presence of concomitant cell-mediated immunity.
D000818:Animals; D000939:Epitopes; D006790:Host-Parasite Interactions; D006801:Humans; D008262:Macrophage Activation; D008264:Macrophages / Q000469:parasitology / Q000502:physiology; D051379:Mice; D009895:Opsonin Proteins / Q000494:pharmacology; D010586:Phagocytes / Q000469:parasitology*; D010587:Phagocytosis; D014349:Trypanosoma cruzi / Q000276:immunology / Q000502:physiology*; D014357:Trypsin / Q000494:pharmacology
D000939:Epitopes; D009895:Opsonin Proteins; D014357:Trypsin