Developmentally-regulated virulence factors of Trypanosoma cruzi and their relationship to evasion of host defences.
Developmental preadaptation of virulent stages of Trypanosoma cruzi correlates with their ability to survive and establish infection in mammalian hosts. Infective trypomastigote stages must first preadapt to survival in the extracellular milieu and then to the rigors of establishing an intracellular infection. Selected phenotypic variations in evading host defences have been correlated with expression of stage-specific proteins or functions. Resistance of trypomastigotes to complement-mediated killing correlates with the presence of a stage-specific molecule that exhibits an analogous function to mammalian decay-accelerating factor, and with the presence of a neuraminidase/trans-sialidase that transfers sialic acid moieties to the parasite surface, thereby enabling it to avoid complement activation. Trypomastigotes enter cells by a mechanism that involves sorting of cell surface receptors and avoids eliciting a respiratory burst. Once within a membrane-bound vacuole, which undergoes acidification, the neuraminidase/trans-sialidase and an acid-active, transmembrane pore-forming protein are released by the parasite and are capable of acting together to accelerate rupture of the vacuolar membrane and the parasite's escape into the cytoplasm of the host cell. Escape from the parasitophorous vacuole allows virulent stages of T. cruzi to avoid compartmental, non-oxidative killing mechanisms such as degradation by lysosomal hydrolases.
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Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510-8056.
Joiner
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D000818:Animals; D006023:Glycoproteins; D006801:Humans; D008954:Models, Biological; D009439:Neuraminidase / Q000378:metabolism; D015800:Protozoan Proteins / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity*; D014774:Virulence
D006023:Glycoproteins; D015800:Protozoan Proteins; C069715:trans-sialidase; D009439:Neuraminidase