Trypanosoma cruzi surface molecule gp90 downregulates invasion of gastric mucosal epithelium in orally infected mice

Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, R. Botucatu, 862- 6 andar, 04023-062 São Paulo, SP, Brazil.
Microbes and Infection (Impact Factor: 2.86). 02/2006; 8(1):36-44. DOI: 10.1016/j.micinf.2005.05.016
Source: PubMed


Experiments were performed to elucidate why Trypanosoma cruzi isolates 573 and 587 differ widely in their efficiency to infect gastric mucosal epithelium when administered orally to mice. These isolates have the same surface profile and a similar capacity to enter host cells in vitro. Metacyclic forms of isolates 573 and 587 and the control CL isolate expressed similar levels of gp82, which is a cell invasion-promoting molecule. Expression of gp90, a molecule that downregulates cell invasion, was lower in the CL isolate. Consistent with this profile, approximately threefold fewer parasites of isolates 573 and 587 entered epithelial HeLa cells, as compared to the CL isolate. No difference in the rate of intracellular parasite replication was observed between isolates. When given orally to mice, metacyclic forms of isolate 573, like the CL isolate, produced high parasitemia (>10(6) parasites per ml at the peak), killing approximately 40% of animals, whereas infection with isolate 587 resulted in low parasitemia (<10(5) parasites per ml), with zero mortality. On the fourth day post-inoculation, tissue sections of the mouse stomach stained with hematoxylin and eosin showed a four to sixfold higher number of epithelial cells infected with isolate 573 or CL than with isolate 587. The rate of intracellular parasite development was similar in all isolates. Mimicking in vivo infection, parasites were treated with pepsin at acidic pH and then assayed for their ability to enter HeLa cells or explanted gastric epithelial cells. Pepsin extensively digested gp90 from isolate 573 and significantly increased invasion of both cells, but had minor effect on gp90 or infectivity of isolates 587 and CL. The profile of g82 digestion was similar in isolates 573 and 587, with partial degradation to a approximately 70 kDa fragment, which preserved the target cell binding domain as well as the region involved in gastric mucin adhesion. Gp82 from CL isolate was resistant to pepsin. Assays with parasites recovered from the mouse stomach 2 h after oral infection showed an extensive digestion of gp90 and increased infectivity of isolate 573, but not of isolate 587 or CL. Our data indicate that T. cruzi infection in vitro does not always correlate with in vivo infection because host factors may act on parasites, modulating their infectivity, as is the case of pepsin digestion of isolate 573 gp90.

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Available from: Anis Rassi, Dec 22, 2014
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    • "Thus, the establishment of T. cruzi infection depends on a series of events involving interactions between the parasite and the host. First, the parasite infects the host cell, either by active penetration [7] or by T. cruzi-host cell phagocytosis [8]. Subsequently, the parasite develops and spreads to these cells and may also modulate the cells' biology. "
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    ABSTRACT: Dendritic cells (DCs) are major immune components, and depending on how these cells are modulated, the protective host immune response changes drastically. Trypanosoma cruzi is a parasite with high genetic variability and modulates DCs by interfering with their capacity for antigen recognition, migration, and maturation. Despite recent efforts, the association between DCs and T. cruzi I (TcI) and TcII populations is unknown. Herein, it was demonstrated that AQ1.7 and MUTUM TcI strains present low rates of invasion of bone marrow-derived DCs, whereas the 1849 and 2369 TcII strains present higher rates. Whereas the four strains similarly induced the expression of PD-L1, the production and expression of IL-10 and TLR-2, respectively, in DCs were differentially increased. The production of TNF-α, IL-12, IL-6, and CCL2 and the expression of CD40, CD80, MHC-II, CCR5, and CCR7 changed depending on the strain. The 2369 strain yielded the most remarkable results because greater invasion correlated with an increase in the levels of anti-inflammatory molecules IL-10 and PD-L1 but not with a change in the levels of TNF-α, MHC-II, or CD40 molecules. These results suggest that T. cruzi strains belonging to different populations have evolved specific evasion strategies that subvert DCs and consequently the host response.
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    • "The possibility that blood trypomastigotes were more susceptible to pepsin digestion at acidic pH was tested using TCT. Lysis of TCT by pepsin at acidic pH was higher than 90% whereas MT preserved their morphology and motility, in the same manner as MT recovered from the mouse stomach 1 hour after oral infection [21]. If the blood trypomastigotes resisted peptic digestion, it is possible that they would be able to overcome the gastric mucin barrier. "
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    • "These are questions that remain to be elucidated. Different T. cruzi strains may vary greatly in their infectivity in vitro and in vivo, and these differences are associated with the differential engagement of surface molecules and triggering of distinct signaling pathways in both cells (Neira et al., 2002; Ferreira et al., 2006; Cortez et al., 2006a; Covarrubias et al., 2007). For instance, strains G (TcI) and CL (TcVI), belonging to highly divergent genetic groups and associated with marsupial and human infection, respectively (Briones et al., 1999), are characterized by their differential infectivity toward cultured mammalian cells as well as in mice (Yoshida, 2006). "
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