Endothelial cell signalling induced by trans-sialidase from Trypanosoma cruzi

Abstract

SummaryThe protozoan responsible for Chagas' disease, Trypanosoma cruzi, expresses on its surface an unusual trans-sialidase enzyme thought to play an important role in host-parasite interactions. Trans-sialidase is the product of a multigene family encoding both active and inactive proteins. We have demonstrated that despite lacking enzymatic activity due to a single mutation, Tyr342-His, inactive trans-sialidase displays sialic acid binding activity, with identical specificity to that of its active analogue. In this work we demonstrate that binding of a recombinant inactive trans-sialidase to molecules containing a2,3-linked sialic acid on endothelial cell surface triggers NF-kB activation, expression of adhesion molecules and upregulation of parasite entry into host cells. Furthermore, inactive recombinant trans-sialidase blocks endothelial cell apoptosis induced by growth factor deprivation. These results suggest that inactive members of the trans-sialidase family play a role in endothelial cell responses to T. cruzi infection.

Trypanosoma cruzi Infection Induces a Global Host Cell Response in Cardiomyocytes

“…PDNF in the cytosol of the host cell apparently activates Akt signaling, leading to a suppression of apoptosis (10). Furthermore, T. cruzi trans-sialidase binds to endothelial cells, triggering activation of NF-B and leading to protection against apoptosis caused by growth factor deprivation (13).…”

Trypanosoma cruzi Subverts Host Cell Sialylation and May Compromise Antigen-specific CD8+ T Cell Responses

“…The TS activity is capable of extensively remodeling the T. cruzi cell surface by using host glycoconjugates as sialyl donors (17,18). Alternatively, the enzyme may sialylate host cell glycomolecules involved in host immune responses (19) and cell invasion (20).…”

The Gp85 Surface Glycoproteins from Trypanosoma cruzi

“…cruzi is controversial. In addition to the carbohydrate-binding site present in the catalytic pocket of the inactive TS implicated in the infectivity of the parasite (Mendonça- Previato et al 2005 ;Souza et al 2010 ;Rubin and Schenkman 2012 ), binding to cell receptors due to the lectin-like domain was also reported for TS, as the nerve growth factor receptor (Trk) (Chuenkova and Pereira Perrin 2005 ; de Melo-Jorge and Dias et al 2008 ;Weinkauf et al 2011 ). Notwithstanding, due to the high number of Gp85/TS proteins displaying extensive polymorphism, it is not unlikely that different members of the superfamily can perform different functions on a complex biological phenomenon, such as parasite adhesion to host cells.…”