Since the pioneering studies by Herta Meyer and co-workers that initiated in vitro studies of T. cruzi development within cultured cells (Meyer and Xavier de Oliveira 1948) followed by the detailed description provided by James Dvorak and Thomas Hyde on how cells become infected by T. cruzi trypomastigotes (Dvorak and Hyde 1973), numerous studies have been performed in order to understand the molecular mechanisms that underlie the rather complex process of parasite entry into mammalian host cells. A number of significant contributions have provided evidence for the participation of both parasite and cellular components. Unfortunately, some of this work have established mechanisms that turned out not to be as universal or general as initially supposed (Ming et al. 1995, Ortega-Barria and Pereira 1991, Tardieux et al. 1992, 1994). On the contrary, it has become increasingly apparent that a rather complex interplay of signaling cascades involving both parasite and cellular components seems to operate (Burleigh and Woolsey 2002, Yoshida 2002). More recently, the discovery of differences in the invasion mechanisms engaged by metacyclic trypomastigotes from the two major phylogenetic lineages of the parasite opened new possibilities to deepen studies on this already intricate process (Neira et al. 2002).
After entering host cells, trypomastigotes are usually found in an acidic membrane-bound compartment referred to as phagosome or parasitophorous vacuole (PV), from where they eventually escape to differentiate into amastigotes in the cytoplasm (Kress et al. 1975, Ley et al. 1990, Meirelles et al. 1986, 1987, 1992, Milder and Kloetzel 1980, Nogueira and Cohn 1976, Tanowitz et al. 1975). In the course of these studies, it became apparent that amastigotes, prematurely released from infected cells or generated by the extracellular differentiation of released tissue-culture derived trypomastigotes (TCTs), could also infect cultured cells and animals (Behbehani 1973, Hudson et al. 1984, Ley et al. 1988, Nogueira and Cohn 1976). Systematic studies on cell invasion and PV escape carried out in our laboratory have reinforced the notion that each infective form of the parasite displays a unique interplay with the specific target host cell with which it interacts. Not only the parasite infective form is relevant but also the strain (and phylogenetic origin) will determine the outcome of the interaction. Furthermore, if target mammalian cells are doubly infected with Coxiella burnetii, the destination and nature of the intracellular compartments that contain T. cruzi infective forms will also be affected. The variety of mechanisms used for invasion and escape from the parasitophorous vacuoles engaged by amastigotes and trypomastigotes is consistent with the complex repertoires of both infective forms and surface molecules that the parasite has evolved to ensure host colonization.