Molecular basis of mammalian cell invasion by Trypanosoma cruzi

Abstract

Establishment of infection by Trypanosoma cruzi, the agent of Chagas´disease, depends on a series of events involving interactions of diverse parasite molecules with host components. Here we focus on the mechanisms of target cell invasion by metacyclic trypomastigotes (MT) and mammalian tissue culture trypomastigotes (TCT). During MT or TCT internalization, signal transduction pathways are activated both in the parasite and the target cell, leading to Ca 2+ mobilization. For cell adhesion, MT engage surface glycoproteins, such as gp82 and gp35/50, which are Ca 2+ signal-inducing molecules. In T. cruzi isolates that enter host cells in gp82-mediated manner, parasite protein tyrosine kinase as well as phospholipase C are activated, and Ca 2+ is released from IP 3 -sensitive stores, whereas in T. cruzi isolates that attach to target cells mainly through gp35/50, the signaling pathway involving adenylate cyclase appears to be stimulated, with Ca 2+ release from acidocalciosomes. In addition, T. cruzi isolate-dependent inhibitory signals, mediated by MT-specific gp90, may be triggered both in the host cell and the parasite. The repertoire of TCT molecules implicated in cell invasion includes surface glycoproteins of gp85 family, with members containing binding sites for laminin and cytokeratin 18, enzymes such as cruzipain, trans-sialidase, and an oligopeptidase B that generates a Ca 2+ -agonist from a precursor molecule.Key words: Trypanosoma cruzi, trypomastigotes, cell invasion, signal transduction, Ca 2+ mobilization. OVERVIEWTrypanosoma cruzi is transmitted by insect vectors when these blood-sucking triatomines deposit on the skin their feces containing MT, the infective forms of the parasite. Through the ocular mucosa or lesions in the skin, the parasites find their way to invade host cells. Metacyclic forms may enter mammalian hosts also by oral route. According to Coura et al. (2002), more than half of the acute cases of Chagas disease recorded between 1968 and 2000 in Brazilian Amazon can be attributed to microepidemics of orally E-mail: nyoshida@ecb.epm.br transmitted infection from contaminated food. The potential sources of contamination are whole triatomine insects or their feces containing infective parasites. Hoft (1996) has shown that MT are efficient in establishing infection in mice when given orally. They enter the gastric mucosal epithelium, transform into amastigotes and replicate intracellularly (Hoft et al. 1996) Mammalian cell invasion by T. cruzi has been extensively studied in vitro by using MT cultured in liquid media and TCT, as counterparts of insectborne and bloodstream parasites respectively. Different T. cruzi isolates and a variety of cell types, mostly cells that are not professional phagocytes, have been used (Table I). The picture emerging from these studies is that T. cruzi penetration into host cells is a multi-step process involving various parasite and host cell molecules that, in a concerted series of events, leads to intracellular Ca 2+ mobilization in both cells (Do...

Infection and invasion mechanisms of Trypanosoma cruzi in the congenital transmission of Chagas' disease: A proposal

“…Before their release from the host cells, amastigotes differentiate back into trypomastigotes that invade the blood stream; they may then enter any other nucleated cell. Amastigotes can be grown in cell cultures inside muscle cells, fibroblasts, and macrophages (Morello, et al 1987;Burleigh and Andrews 1995;Yoshida, 2006), from which infecting forms of T. cruzi (trypomastigotes) may be harvested. Chagas' disease develops in three phases.…”

“…Parasite attachment to host cells is receptor mediated. T. cruzi possesses a series of surface molecules that interact in a differential manner with molecules from the host's cells and extracellular matrix (ECM) (Yoshida, 2006). T. cruzi cellular invasion induces calcium signals and activation of signal transduction pathways both in the parasite and the host (Yoshida, 2006;Yoshida 2008).…”

“…T. cruzi possesses a series of surface molecules that interact in a differential manner with molecules from the host's cells and extracellular matrix (ECM) (Yoshida, 2006). T. cruzi cellular invasion induces calcium signals and activation of signal transduction pathways both in the parasite and the host (Yoshida, 2006;Yoshida 2008). The parasite's capacity to generate calcium signals in the host is related to its infectivity (Manque et al 2003, Yoshida 2008.…”

“…Phospholipase C (PLC) activation is one of the most important signal transduction pathways because it generates Inositol-3-phosphate (IP3), which leads to calcium liberation from intracellular deposits (Rodriguez, et al 1995;Yoshida 2006). This increase in calcium induces recruitment (Andrews, 2002) and fusion of lysosomes (Jaiswal, et al 2002) with the plasma membrane at the site of parasite invasion.…”

“…This process is boosted by a concomitant rise in cyclic AMP (Rodriguez, et al 1999). Disorganization of the cytoskeleton is also produced by de-polymerization of actin filaments (Rodriguez, et al 1995;Woolsey and Burleigh 2004;Yoshida, 2006;Yoshida, 2008).…”