Molecular mechanisms of Trypanosoma cruzi infection by oral route.
Frequent reports on outbreaks of acute Chagas' disease by ingestion of food contaminated with parasites from triatomine insects illustrate the importance of this mode of transmission. Studies on oral Trypanosoma cruzi infection in mice have indicated that metacyclic trypomastigotes invade the gastric mucosal epithelium. A key molecule in this process is gp82, a stage-specific surface glycoprotein that binds to both gastric mucin and to target epithelial cells. By triggering Ca2+ signalling, gp82 promotes parasite internalisation. Gp82 is relatively resistant to peptic digestion at acidic pH, thus preserving the properties critical for oral infection. The infection process is also influenced by gp90, a metacyclic stage-specific molecule that negatively regulates the invasion process. T. cruzi strains expressing high gp90 levels invade cells poorly in vitro. However, their infectivity by oral route varies considerably due to varying susceptibilities of different gp90 isoforms to peptic digestion. Parasites expressing pepsin-susceptible gp90 become highly invasive against target cells upon contact with gastric juice. Such is the case of a T. cruzi isolate from an acute case of orally acquired Chagas' disease; the gp90 from this strain is extensively degraded upon short period of parasite permanence in the gastric milieu. If such an exacerbation of infectivity occurs in humans, it may be responsible for the severity of Chagas' disease reported in outbreaks of oral infection.
Yoshida
Nobuko
N
Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, São Paulo, SP, Brasil. nyoshida@unifesp.br
D000818:Animals; D014355:Chagas Disease / Q000469:parasitology / Q000635:transmission*; D004847:Epithelial Cells / Q000469:parasitology; D016266:Food Parasitology; D005753:Gastric Mucosa / Q000469:parasitology*; D006801:Humans; D007303:Insect Vectors / Q000469:parasitology; D051379:Mice; D015800:Protozoan Proteins / Q000502:physiology*; D014349:Trypanosoma cruzi / Q000472:pathogenicity / Q000502:physiology*; D014643:Variant Surface Glycoproteins, Trypanosoma / Q000502:physiology*
D015800:Protozoan Proteins; D014643:Variant Surface Glycoproteins, Trypanosoma; C527132:glycoprotein GP82, Trypanosoma cruzi; C044186:glycoprotein GP90, Trypanosoma cruzi