Differential expression of pathogenic genes of Entamoeba histolytica vs E. dispar in a model of infection using human liver tissue explants
Por:
Ximénez C., González E., Nieves M., Magaña U., Morán P., Gudiño-Zayas M., Partida O., Hernández E., Rojas-Velázquez L., García de León M.C., Maldonado H.
Publicada:
3 ago 2017
Resumen:
We sought to establish an ex vivo model for examining the interaction of
E. histolytica with human tissue, using precision-cut liver slices
(PCLS) from donated organs. E. histolytica-or E. dispar-infected PCLS
were analyzed at different post-infection times (0, 1, 3, 24 and 48 h)
to evaluate the relation between tissue damage and the expression of
genes associated with three factors: a) parasite survival
(peroxiredoxin, superoxide dismutase and 70 kDa heat shock protein), b)
parasite virulence (EhGal/GalNAc lectin, amoebapore, cysteine proteases
and calreticulin), and c) the host inflammatory response (various
cytokines). Unlike E. dispar (non-pathogenic), E. histolytica produced
some damage to the structure of hepatic parenchyma. Overall, greater
expression of virulence genes existed in E. histolytica-infected versus
E. dispar-infected tissue. Accordingly, there was an increased
expression of EhGal/GalNAc lectin, Ehap-a and Ehcp-5, Ehcp-2, ehcp-1
genes with E. histolytica, and a decreased or lack of expression of
Ehcp-2, and Ehap-a genes with E. dispar. E. histolytica-infected tissue
also exhibited an elevated expression of genes linked to survival,
principally peroxiredoxin, superoxide dismutase and Ehhsp-70. Moreover,
E. histolytica-infected tissue showed an overexpression of some genes
encoding for pro-inflammatory interleukins (ILs), such as il-8,
ifn-gamma and tnf-alpha Contrarily, E. dispar-infected tissue displayed
higher levels of il-10, the gene for the corresponding anti-inflammatory
cytokine. Additionally, other genes were investigated that are important
in the host-parasite relationship, including those encoding for the 20
kDa heat shock protein (HSP-20), the AIG-1 protein, and immune dominant
variable surface antigen, as well as for proteins apparently involved in
mechanisms for the protection of the trophozoites in different
environments (e.g., thiore-doxin-reductase, oxido-reductase, and 9
hypothetical proteins). Some of the hypothetical proteins evidenced
interesting overexpression rates, however we should wait to their
characterization. This finding suggest that the present model could be
advantageous for exploring the complex interaction between trophozoites
and hepatocytes during the development of ALA, particularly in the
initial stages of infection.
Filiaciones:
Ximénez C.:
Laboratory of Immunology, Unit of Experimental Medicine, Faculty of Medicine, UNAM, México City, Mexico
González E.:
Laboratory of Immunology, Unit of Experimental Medicine, Faculty of Medicine, UNAM, México City, Mexico
Nieves M.:
Laboratory of Immunology, Unit of Experimental Medicine, Faculty of Medicine, UNAM, México City, Mexico
Magaña U.:
Laboratory of Immunology, Unit of Experimental Medicine, Faculty of Medicine, UNAM, México City, Mexico
Morán P.:
Laboratory of Immunology, Unit of Experimental Medicine, Faculty of Medicine, UNAM, México City, Mexico
Gudiño-Zayas M.:
Laboratory of Immunology, Unit of Experimental Medicine, Faculty of Medicine, UNAM, México City, Mexico
Partida O.:
Laboratory of Immunology, Unit of Experimental Medicine, Faculty of Medicine, UNAM, México City, Mexico
Hernández E.:
Laboratory of Immunology, Unit of Experimental Medicine, Faculty of Medicine, UNAM, México City, Mexico
Rojas-Velázquez L.:
Laboratory of Immunology, Unit of Experimental Medicine, Faculty of Medicine, UNAM, México City, Mexico
García de León M.C.:
Unit of Scientific Vinculation, Faculty of Medicine, UNAM/INMEGEN, México City, Mexico
Maldonado H.:
Sub direction of Pathology, National Institute of Cancerology, México City, Mexico
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