Trypanosoma cruzi: mechanism of entry and intracellular fate in mammalian cells.

Abstract

The factors involved in the resistance or susceptibility of mammalian hosts to infection with Trypanosoma cruzi remain obscure. A more detailed analysis of the interactions of the parasite and host cells would provide a better understanding of the pathogenesis of this infection. Several investigators have examined the mode of entry, intracellular development, and fate of T. cruzi in a variety of cells using both light and electron microscopic techniques, but the result of these studies are contradictory (1-11).We report here our studies on the mode of entry and fate of both epimastigote and trypomastigote forms ofT. cruzi at the light and electron microscope levels. The observations were mainly performed with mouse peritoneal macrophages, although parallel studies on several cultured cell types (HeLa, L cells, calf embryo fibroblasts) will also be described. Utilizing a technique to separate the cultured forms of epimastigotes and trypornastigotes (12), we were then able to study their different fates as well as the components of the host cell plasma membrane involved in the interiorization process. Some of these results have been previously published in abstract form (13).

The use of confocal laser scanning microscopy to analyze the process of parasitic protozoon-host cell interaction

“…It is important to point out, however, that in the case of T. cruzi this membrane has a short life span since it is completely lysed a few hours after its formation (12)(13)(14).…”

“…For some parasites, such as T. gondii, a special PV which does not fuse with components of the endo-lysosomal pathway of the host cell is an ideal site for parasite replication (8)(9)(10)(11). Other parasites, such as T. cruzi, must lyse the membrane lining the PV and enter into direct contact with the cytoplasmic structures of the host cell in order to start the process of division (12)(13)(14). Despite the importance of the PV, little information is available about the basic aspects related to its formation.…”

Morphological comparison of axenic amastigogenesis of trypomastigotes and metacyclic forms of Trypanosoma cruzi

“…Most of the information concerning the in vitro and in vivo amastigogenesis process comes from the study of tissue-derived trypomastigote forms (Nogueira & Cohn 1976, Milder et al 1977, Ley et al 1988, Burleigh & Andrews 1995, Barros et al 1996, 1997, but little is known about the developmental process driving the metacyclic forms to amastigotes. Although, metacyclic trypomastigotes can appear similar in morphology and share some biological properties with tissue-derived trypomastigotes.…”

Why studies on invasion of host cell by Trypanosoma cruzi using stablished cell lines or primary cell cultures give conflicting results?

“…One of the points that remains under discussion, mainly in the last 10 years, has been the mechanism of invasion of phagocytic and non-professional phagocytic cells by T. cruzi. A series of papers have reported that cytochalasins B (CB) and D (CD) block the entry of epimastigotes and trypomastigotes into macrophages, Vero cells and fibroblasts (Alexander 1975, Nogueira & Cohn 1976, Ebert & Barbosa 1981, Henriquez et al 1981, Meirelles et al 1982, Zenian & Kierszenbaum 1983, while others have reported active penetration of trypomastigote forms into CB-treated fibroblasts, MDCK and HeLa cells (Schenkman et al 1991, Schenkman & Mortara 1992. Amastigote forms, on the other hand, invade HeLa cells after association with surface microvilli and mobilization of actin microfilaments (Mortara 1991).…”