Oral infectivity through carnivorism in murine model of Trypanosoma cruzi infection
Cargando...
Fecha
2024
Título de la revista
ISSN de la revista
Título del volumen
Editor
Resumen
Introduction: Oral transmission of T. cruzi is probably the most frequent
transmission mechanism in wild animals. This observation led to the hypothesis
that consuming raw or undercooked meat from animals infected with T. cruzi
may be responsible for transmitting the infection. Therefore, the general
objective of this study was to investigate host-pathogen interactions between
the parasite and gastric mucosa and the role of meat consumption from infected
animals in the oral transmission of T. cruzi.
Methods: Cell infectivity assays were performed on AGS cells in the presence or
absence of mucin, and the roles of pepsin and acidic pH were determined.
Moreover, groups of five female Balb/c mice were fed with muscle tissue
obtained from mice in the acute phase of infection by the clone H510
C8C3hvir of T. cruzi, and the infection of the fed mice was monitored by a
parasitemia curve. Similarly, we assessed the infective capacity of T. cruzi
trypomastigotes and amastigotes by infecting groups of five mice Balb/c
females, which were infected orally using a nasogastric probe, and the
infection was monitored by a parasitemia curve. Finally, different
trypomastigote and amastigote inoculums were used to determine their
infective capacities. Adhesion assays of T. cruzi proteins to AGS stomach cells
were performed, and the adhered proteins were detected by western blotting
using monoclonal or polyclonal antibodies and by LC-MS/MS and
bioinformatics analysis.
Results: Trypomastigote migration in the presence of mucin was reduced by
approximately 30%, whereas in the presence of mucin and pepsin at pH 3.5, only
a small proportion of parasites were able to migrate (∼6%). Similarly, the ability of
TCTs to infect AGS cells in the presence of mucin is reduced by approximately
20%. In all cases, 60–100% of the animals were fed meat from mice infected in
the acute phase or infected with trypomastigotes or amastigotes developed high parasitemia, and 80% died around day 40 post-infection. The adhesion assay
showed that cruzipain is a molecule of trypomastigotes and amastigotes that
binds to AGS cells. LC-MS/MS and bioinformatics analysis, also confirmed that
transialidase, cysteine proteinases, and gp63 may be involved in TCTs attachment
or invasion of human stomach cells because they can potentially interact with
different proteins in the human stomach mucosa. In addition, several human
gastric mucins have cysteine protease cleavage sites.
Discussion: Then, under our experimental conditions, consuming meat from
infected animals in the acute phase allows the T. cruzi infection. Similarly,
trypomastigotes and amastigotes could infect mice when administered orally,
whereas cysteinyl proteinases and trans-sialidase appear to be relevant
molecules in this infective process.