Please use this identifier to cite or link to this item:
Type
ArticleCopyright
Open access
Collections
- IOC - Artigos de Periódicos [12659]
Metadata
Show full item record
CRUZIPAIN ACTIVATES LATENT TGF-β FROM HOST CELLS DURING T. CRUZI INVASION
Author
Affilliation
Abstract
Several studies indicate that the activity of cruzipain, the main lysosomal cysteine peptidase
of Trypanosoma cruzi, contributes to parasite infectivity. In addition, the parasitic invasion
process of mammalian host cells is described to be dependent on the activation of the host
TGF-β signaling pathway by T. cruzi. Here, we tested the hypothesis that cruzipain could be
an important activator of latent TGF-β and thereby trigger TGF-β-mediated events crucial
for the development of Chagas disease. We found that live epimastigotes of T. cruzi, parasite
lysates and purified cruzipain were able to activate latent TGF-β in vitro. This activation
could be inhibited by the cysteine peptidase inhibitor Z-Phe-Ala-FMK. Moreover, transfected
parasites overexpressing chagasin, a potent endogenous cruzipain inhibitor, prevented
latent TGF-β activation. We also observed that T. cruzi invasion, as well as parasite
intracellular growth, were inhibited by the administration of Z-Phe-Ala-FMK or anti-TGF-β
neutralizing antibody to Vero cell cultures. We further demonstrated that addition of purified
cruzipain enhanced the invasive activity of trypomastigotes and that this effect could be
completely inhibited by addition of a neutralizing anti-TGF-β antibody. Taken together,
these results demonstrate that the activities of cruzipain and TGF-β in the process of cell invasion
are functionally linked. Our data suggest that cruzipain inhibition is an interesting
chemotherapeutic approach for Chagas disease not only because of its trypanocidal activity,
but also due to the inhibitory effect on TGF-β activation.
Share