Abstract
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-β receptor or integrin family member may also be triggered by TCT. A more complete and detailed picture of T. cruzi invasion needs further investigations.
Chapter PDF
Similar content being viewed by others
Keywords
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
References
Docampo R, Moreno SJ. The role of Ca2+ in the process of cell invasion by intracellular parasites. Parasitol Today 1996; 12:61–65.
Burleigh BA, Andrews NW. Signaling and host cell invasion by Trypanosoma cruzi. Curr Opinion Microbiol 1998; 1:451–465.
Yoshida N. Molecular basis of mammalian cell invasion by Trypanosoma cruzi. Anals Braz Acad Sci 2005; 77:26.
Ruiz RC, Favoreto S, Dorta ML et al. Infectivity of Trypanosoma cruzi strains is associated with differential expression of surface glycoproteins with differential Ca2+ signaling activity. Biochem J 1998; 330:505–511.
Ramirez MI, Ruiz RC, Araya JE et al. Involvement of the stage-specific 82-kilodalton adhesion molecule of Trypanosoma cruzi metacyclic trypomastigotes in host cell invasion. Infect Immun 1993; 61:3636–3641.
Ruiz RC, Rigoni VL, Gonzalez J et al. The 35/50 kDa surface antigen of Trypanosoma cruzi metacyclic trypomastigotes, an adhesion molecule involved in host cell invasion. Parasite Immunol 1993; 15:121–123.
Yoshida N, Mortara RA, Araguth MF et al. Metacyclic neutralizing effect of monoclonal antibody 10D8 directed to the 35-and 50-kilodalton surface glycoconjugates of Trypanosoma cruzi. Infect Immun 1998; 57:1663–1667.
Cortez M, Neira I, Ferreira D et al. Infection by Trypanosoma cruzi metacyclic forms deficient in gp82 but expressing a related surface molecule gp30. Infect Immun 2003; 71:6184–6191.
Cardoso de Almeida ML, Heise N. Proteins anchored via glycosylphosphatidylinositol and solubilizing phospholipases in Trypanosoma cruzi. Biol Res 1993; 26:285–312.
Manque PM, Eichinger D, Juliano MA et al. Characterization of the cell adhesion site of Trypanosoma cruzi metacyclic stage surface glycoprotein gp82. Infect Immun 2000; 68:478–484.
Yoshida N, Favoreto Jr S, Ferreira AT et al. Signal transduction induced in Trypanosoma cruzi metacyclic trypomastigotes during the invasion of mammalian cells. Braz J Med Biol Res 2000; 33:269–278.
Favoreto Jr S, Dorta ML, Yoshida N. Trypanosoma cruzi 175 kDa protein tyrosine phosphorylation is associated with host cell invasion. Exp Parasitol 1998; 89:188–194.
Atayde VD, Neira I, Cortez M et al. Molecular basis of non virulence of Trypanosoma cruzi clone CL-14. Int J Parasitol 2004; 34:851–860.
Teixeira MMG, Yoshida N. Stage-specific surface antigens of metacyclic trypomastigotes of Trypanosoma cruzi identified by monoclonal antibodies. Mol Biochem Parasitol 1986; 18:271–282.
Schenkman S, Ferguson MAJ, Heise N et al. Mucin-like glycoproteins linked to the membrane by glycosylphosphatidylinositol anchor are the major acceptors of sialic acid in a reaction catalysed by trans-sialidase in metacyclic forms of Trypanosoma cruzi. Mol Biochem Parasitol 1993; 59:293–304.
Schenkman S, Jiang M, Hart GW et al. A novel cell surface trans-sialidase of Trypanosoma cruzi generates a stage-specific epitope required for invasion of mammalian cells. Cell 1991; 65:1117–1125.
Yoshida N, Dorta ML, Ferreira AT et al. Removal of sialic acid from mucin-like surface molecules of Trypanosoma cruzi metacyclic trypomastigotes enhances parasite-host cell interaction. Mol Biochem Parasitol 1997; 84:57–67.
Neira I, Ferreira AT, Yoshida N. Activation of distinct signal transduction pathways in Trypanosoma cruzi isolates with differential capacity to invade host cells. Int J Parasitol 2002; 32:405–414.
Docampo R, Scott DA, Vercesi AE et al. Intracellular Ca2+ storage in acidocalcisomes of Trypanosoma cruzi. Biochem J 1995; 310:1005–1012.
Giordano R, Chammas R, Veiga SS et al. An acidic component of the heterogeneous Tc-85 protein family from the surface of Trypanosoma cruzi is a laminin binding glycoprotein. Mol Biochem Parasitol 1994; 65:85–94.
Magdesian MH, Giordano R, Juliano MA et al. Infection by Trypanosoma cruzi: Identification of a parasite ligand and its host-cell receptor. J Biol Chem 2001; 276:19382–19389.
Rodriguez A, Rioult MG, Ora A et al. A trypanosome-soluble factor induces IP3 formation, intracellular Ca2+ mobilization and microfilament rearrangement in host cells. J Cell Biol 1995; 129:1263–1273.
Burleigh B, Caler EV, Webster P et al. A cytosolic serine endopeptidase from Trypanosoma cruzi is required for the generation of Ca2+ signaling in mammalian cells. J Cell Biol 1997; 136:609–620.
Caler EV, Vaena de Avalos S, Haynes PA et al. Oligopeptidase B-dependent signaling mediates host cell invasion by Trypanosoma cruzi. EMBO J 1998; 17:4975–4986.
Meirelles MN, Juliano L, Carmona E et al. Inhibitors of the major cysteinyl proteinase (gp57/51) impair host cell invasion and arrest the intracellular development of Trypanosoma cruzi in vivo. Mol Biochem Parasitol 1992; 52:175–184.
Scharfstein J, Schmitz V, Morandi V et al. Host cell invasion by Trypanosoma cruzi is potentiated by activation of bradykinin B2 receptors. J Exp Med 2000; 192:1289–1299.
Lima APCA, Almeida PC, Tersariol ILS et al. Heparan sulfate modulates kinin release by Trypanosoma cruzi through the activity of cruzipain. J Biol Chem 2002; 277:5875–5881.
Ming M, Ewen ME, Pereira MEA. Trypanosome invasion of mammalian cells requires activation of the TGFβ signaling pathway. Cell 1995; 82:287–296.
Fernandez MA, Munoz-Fernandez MA, Fresno M. Involvement of beta 1 integrins in the binding and entry of Trypanosoma cruzi into human macrophages. Eur J Immunol 1993; 23:552–557.
Elad-Sfadia G, Haklai R, Balan E et al. Galectin-3 augments K-Ras activation and triggers a Ras signal that attenuates ERK but not phosphoinositide 3-kinase activity. J Biol Chem 2004; 279:34922–34930.
Kleshchenko YY, Moody TN, Furtak VA et al. Human galectin-3 promotes Trypanosoma cruzi adhesion to human artery smooth muscle cells. Infect Immun 2004; 72:6717–6721.
Vieira MCF, Carvalho TU, Souza W. Effect of protein kinase inhibition on the invasion process of macrophages by Trypanosoma cruzi. Biochem Biophys Res Commun 1994; 203:967–971.
Vieira M, Dutra JM, Carvalho TM et al. Cellular signaling during the macrophage invasion by Trypanosoma cruzi. Histochem Cell Biol 2002; 118:491–500.
Villalta F, Zhang Y, Bibb KE et al. Signal transduction in human macrophages by gp83 ligand of Trypanosoma cruzi: Trypomastigote gp83 ligand up-regulated trypanosome entry through protein kinase C activation. Mol Cell Biol Res Commun 1999; 2:64–70.
Wilkowsky SE, Barbieri MA, Stahl P et al. Trypanosoma cruzi phosphatidylinositol 3-kinase and protein kinase B activation is associated with parasite invasion. Exp Cell Res 2001; 264:211–218.
Zhong L, Lu HG, Moreno SN et al. Tyrosine phosphate hydrolysis of host proteins by Trypanosoma cruzi is linked to cell invasion. FEMS Microbiol Lett 1998; 161:15–20.
Sartori MJ, Mezzano L, Lin S et al. Role of placental alkaline phosphatase in the internalization of trypomastigotes of Trypanosoma cruzi into HEp2 cells. Trop Med Int Health 2003; 8:832–839.
Todorov AG, Einicker-Lamas M, Castro SL et al. Activation of host cell phosphatidylinositol 3-ki-nases by Trypanosoma cruzi infection. J Biol Chem 2000; 275:32182–32186.
Tardieux I, Webster P, Ravesloot J et al. Lysosome recruitment and fusion are early events required for Trypanosoma invasion of mammalian cells. Cell 1992; 71:1117–1130.
Rodriguez A, Martinez I, Chung A et al. cAMP regulates Ca2+-dependent exocytosis of lysosomes and lysosome-mediated cell invasion by trypanosomes. J Biol Chem 1999; 274:6754–16759.
Caler EV, Chakrabarti S, Fowler KT et al. The exocytosis-regulatory protein sinaptotagmin VII mediates cell invasion by Trypanosoma cruzi. J Exp Med 2001; 193:1097–1104.
Woolsey AM, Sunwoo L, Petersen CA et al. Novel PI 3-kinase-dependent mechanisms of trypanosome invasion and vacuole maturation. J Cell Sci 2003; 116:3611–3622.
Wilkowsky SE, Barbieri MA, Stahl P et al. Regulation of Trypanosoma cruzi invasion of nonphagocytic cells by the endocytically active GTPases dynamin, Rab5, and Rab7. Biochem Biophys Res Commun 2002; 291:516–521.
Andrade LO, Andrews NW. Lysosomal fusion is essential for the retention of Trypanosoma cruzi inside host cells. J Exp Med 2004; 200:1135–1143.
Woolsey AM, Burleigh B. Host cell actin polymerization is required for cellular retention of Trypanosoma cruzi and early association with endosomal/lysosomal compartments. Cell Microbiol 2004; 6:829–838.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2008 Landes Bioscience and Springer Science+Business Media
About this chapter
Cite this chapter
Yoshida, N., Cortez, M. (2008). Trypanosoma cruzi: Parasite and Host Cell Signaling during the Invasion Process. In: Burleigh, B.A., Soldati-Favre, D. (eds) Molecular Mechanisms of Parasite Invasion. Subcellular Biochemistry, vol 47. Springer, New York, NY. https://doi.org/10.1007/978-0-387-78267-6_6
Download citation
DOI: https://doi.org/10.1007/978-0-387-78267-6_6
Publisher Name: Springer, New York, NY
Print ISBN: 978-0-387-78266-9
Online ISBN: 978-0-387-78267-6
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)