Trypanosoma cruzi: parasite and host cell signaling during the invasion process.
Mammalian cell invasion by Trypanosoma cruzi is a complex process in which various parasite and host cell components interact, triggering the activation of signaling cascades and Ca2+ mobilization in both cells. Using metacyclic trypomastigotes (MT) generated in vitro and tissue culture-derived trypomastigotes (TCT), as counterparts of insect-borne and bloodstream parasites, respectively, the mechanisms of host cell invasion by T. cruzi have been partially elucidated. Distinct sets of molecules are engaged by MT and TCT to enter target cells. MT make use of surface glycoproteins with dual Ca2+ signaling activity, in a manner dependent of T. cruzi isolate. In highly infective MT, the binding of gp82 to its receptor triggers a signaling cascade involving protein tyrosine kinase, phospholipase C and production of inositol 1,4,5-triphosphate, whereas in poorly invasive MT, the mucin-like gp35/50 induces the activation of a signaling route in which adenylate cyclase, generation of cAMP and Ca2+ mobilization from acidocalcisomes are implicated. The host cell signaling pathways activated by MT remain to be determined. Differently from MT, the TCT surface molecules that bind to host cells as a prelude to invasion, such as the glycoproteins of gp85 family, appear to be devoid of signaling properties, but they may induce TCT enzymes, such as oligopeptidase B and cruzipain, to generate Ca2+ signaling factors of parasite or host cell origin. Host cell responses mediated by TGF-beta receptor or integrin family member may also be triggered by TCT. A more complete and detailed picture of T. cruzi invasion needs further investigations.
Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, R. Botucatu, 862, 04023-062 São Paulo, SP, Brasil. nyoshida@ecb.epm.br
Nobuko
N
Yoshida
Mauro
M
Cortez
D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D006790:Host-Parasite Interactions / Q000235:genetics / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D015398:Signal Transduction; D014349:Trypanosoma cruzi / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity* / Q000502:physiology*