Trypanosoma cruzi-fibroblastic cell interactions necessary for cellular invasion

Abstract

Detailed knowledge of the mechanism by which vertebrate cells are invaded by the haemoflagellated parasite Trypanosoma cruzi is of paramount importance for understanding one of the early events in the life cycle of this obligatory intracellular parasite. The ability to infect vertebrate fibroblastic cells was found to be only partially expressed in trypomastigotes that were recently liberated from cell cultures. These trypomastigotes could increase by several fold their capability for adhesion and infection by a time-dependent in vitro process. This activation phenomenon was used to study how certain inhibitors of macromolecular biosynthesis (actinomycin D, puromycin, tunicamycin), proteases, protease inhibitors, and a combination of them, acted on adhesion and infection. The effect of exposing the parasites and, independently, the host fibroblasts to various lectins and carbohydrates was also investigated. Most of these treatments either inhibited or stimulated adhesion and infection. Exposure of fibroblastic cells to trypsin and to drugs altering the cytoskeleton impaired their susceptibility to infection. Tunicamycin blocked the recovery of infection, but not of adhesion, in trypsinized cells. The results obtained have been interpreted as indicating that the process of fibroblast infection by T. cruzi trypomastigotes occurs through two distinct and independent steps (adhesion and penetration), mediated by components of both the parasite and the host cell. The parasite components seem to be: (a) a lectin-like protein involved in adhesion; (b) an activating inducible system, probably of proteolytic nature, which enhances parasite adhesion; and (c) a tunicamycin-sensitive glycoprotein, related to penetration only. As for the fibroblastic cell components, these are postulated to be two glycoproteins (one insensitive and the other sensitive to tunicamycin), which are involved in the steps of parasite attachment and penetration, respectively.