Skip to main content
SpringerLink
Log in
Book cover

Biology of Parasitism pp 195–212Cite as

Lysosome Exocytosis and Invasion of Non-Phagocytic Host Cells by Trypanosoma Cruzi

  • Chapter

Abstract

In recent years, significant progress has been made toward understanding the mechanisms of host cell invasion by the intracellular pathogen, Trypanosoma cruzi. Invasion of non-phagocytic cells by trypomastigotes, the mammalianinfective forms of T. cruzi, is achieved by a surprising mechanism whereby host cell lysosomes are recruited as a vehicle for parasite entry. These studies have revealed the existence of the lysosome exocytosis pathway, a previously unrecognised regulated secretion system in non-phagocytic mammalian cells. Host cell signalling pathways that regulate T. cruzi entry and lysosome recruitment were shown to involve the second messengers, Ca2+ and cAMP and require secreted agonist(s) generated by the parasite. In addition, the ability of T. cruzi to receive signals from the host cell in a contact-dependent manner is crucial to the invasive process. In this chapter, I will outline our current knowledge of the cellular and molecular bases for host cell invasion by T. cruzi as well as the experimental approaches taken to study this process.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Andrews, N.W., Abrams, C.K., Slatin, S.L. and Griffiths, G. (1990). A T. cruzi-secreted protein immunologically related to the complement component C9: evidence for membrane pore-forming activity at low pH. Cell 61, 1277–87.

    Article  PubMed  CAS  Google Scholar 

  • Andrews, N.W. and Whitlow, M.B. (1989). Secretion by Trypanosoma cruzi of a hemolysin active at low pH. Mol. Biochem. Parasitol. 33, 249–256.

    Article  PubMed  CAS  Google Scholar 

  • Baron, R., Neffe, L., Brow, W., Courtoy, P.J., Louvard, D. and Farquhar, M.G. (1988). Polarized secretion of lysosomal enzymes: co-distribution of cation-independent mannose-6-phosphate receptors and lysosomal enzymes along the osteoclast exocytic pathway. J. Cell Biol. 106, 1863–1872.

    Article  PubMed  CAS  Google Scholar 

  • Burgoyne, R.D. and Morgan, A. (1993). Regulated exocytosis. Biochem. J. 293, 305–316. Burgoyne, R.D. and Morgan, A. (1998). Calcium sensors in regulated exocytosis. Cell Calcium 24, 367–376.

    Google Scholar 

  • Burleigh, B. and Andrews, N.W. (1995). A 120 kDa alkaline peptidase from Trypanosoma cruzi is involved in the generation of a novel Cat+ signaling factor for mammalian cells. J. Biol. Chem. 270, 5172–5180.

    Article  PubMed  CAS  Google Scholar 

  • Burleigh, B.A. and Andrews, N.W. (1998). Signaling and host cell invasion by Trypanosoma cruzi. Curr. Opin. Microbiol. 1, 461–465.

    Google Scholar 

  • Burleigh, B.A., Caler, E.V., Webster, P. and Andrews, N.W. (1997). A cytosolic serine endopeptidase from Trypanosoma cruzi is required for the generation of Cat+ signaling in mammalian cells. J. Cell Biol. 136, 609–620.

    Article  PubMed  CAS  Google Scholar 

  • Caler, E.V., Vaena, S., Haynes, P.A., Andrews, N.W. and Burleigh, B.A. (1998). Oligopeptidase B-dependent signaling mediates host cell invasion by Trypanosoma cruzi. EMBO J. 17, 4975–4986.

    Article  PubMed  CAS  Google Scholar 

  • Carvalho, T.M.V. and de Souza, W. (1989). Early events related with the behavior of Trypanosoma cruzi within an endocytic vacuole in mouse peritoneal macrophages. Cell Struct. Funct. 14, 383–392.

    Google Scholar 

  • de Meirelles, M.N., de Araujo Jorge, T.C., de Souza, W., Moreira, A.L. and Barbosa, H.S. (1987). Trypanosoma cruzi: phagolysosomal fusion after invasion into nonprofessional phagocytic cells. Cell Struct. Funct. 12, 387–393.

    Google Scholar 

  • Dorta, M.L., Ferreira, A.T., Oshiro, M.E.M. and Yoshida, N. (1995). Cat+ signal induced by Trypanosoma cruzi metacyclic trypomastigote surface molecules implicated in mammalian cell invasion. Mol. Biochem. Parasitol. 73, 285–289.

    Google Scholar 

  • Dvorak, J.A. and Crane, M.S. (1981). Vertebrate cell cycle modulates infection by protozoan parasites. Science 214, 1034–1036.

    Article  PubMed  CAS  Google Scholar 

  • Furuya, T., Zhong, L., Meyer-Fernandes, J.R., Lu, H.G., Moreno, S.N. and Docampo, R. (1998). Ecto-protein tyrosine phosphatase activity in Trypanosoma cruzi infective stages. Mol. Biochem. Parasitol. 92, 339–348.

    Article  PubMed  CAS  Google Scholar 

  • Grellier, P., Blum, J., Santana, J., Bylen, E., Mouray, E., Sinou, V., Teixeira, A.R. and Schrevel, J. (1999). Involvement of calyculin A-sensitive phosphatase(s) in the differentiation of Trypanosoma cruzi trypomastigotes to amastigotes. Mol. Biochem. Parasitol. 98, 239–252.

    Article  PubMed  CAS  Google Scholar 

  • Hall, B.F., Webster, P., Ma, A.K., Joiner, K.A. and Andrews, N.W. (1992). Desialylation of lysosomal membrane glycoproteins by Trypanosoma cruzi: a role for the surface neuraminidase in facilitating parasite entry into the host cell cytoplasm. J. Exp. Med. 176, 313–325.

    Article  PubMed  CAS  Google Scholar 

  • Heuser, J.E. (1989). Changes in lysosome shape and distribution correlated with changes in cytoplasmic pH. J. Cell Biol. 108, 855–864.

    Article  PubMed  CAS  Google Scholar 

  • Hirano, T., Saluja, A., Ramarao, P., Lerch, M.M., Saluja, M. and Steer, M.L. (1991). Apical secretion of lysosomal enzymes in rabbit pancreas occurs via a secretagogue regulated pathway and is increased after pancreatic duct obstruction. J. Clin. Invest. 87, 865–869.

    Article  PubMed  CAS  Google Scholar 

  • Kipnis, T.L., Calich, V.L.G. and Dias da Silva, W. (1979). Active entry of bloodstream forms of Trypanosoma cruzi into macrophages. Parasitol. 78, 89–99.

    Article  CAS  Google Scholar 

  • Leite, M.F., Moyer, M.S., Nathanson, M.H. and Andrews, N.W. (1998). Expression of the mammalian calcium signaling response to Trypanosoma cruzi in Xenopus laevis oocytes. Mol. Biochem. Parasitol. 92, 1–13.

    Article  PubMed  CAS  Google Scholar 

  • LeSage, G.D., Robertson, W.E. and Baumgart, M.A. (1993). Bile acid-dependent vesicular transport of lysosomal enzymes into bile in the rat. Gastroenterology 105, 889–900.

    PubMed  CAS  Google Scholar 

  • Ley, V., Robbins, E.S., Nessenzweig, V. and Andrews, N.W. (1990). The exit of Trypanosoma cruzi from the phagosome is inhibited by raising the pH of acidic compartments. J. Exp. Med. 1 71, 401–413.

    Article  Google Scholar 

  • Meirelles, M.N.L., Araujo Jorge, T.C. and de Souza, W. (1982). Interaction of Trypanosoma cruzi with macrophages in vitro: dissociation of the attachment and internalization phases by low temperature and cytochalasin B. Z. Prasitenkd 68, 7–14.

    Article  Google Scholar 

  • Meirelles, M.N.L. and de Souza, W. (1983). Interaction of lysosomes with endocytic vacuoles in macrophages simultaneously infected with Trypanosoma cruzi and Toxoplasma gondii. J. Submicrosc. Cytol. Pathol. 17, 327–334.

    Google Scholar 

  • Milder, R. and Kloetzel, J. (1980). The development of Trypanosoma cruzi in macrophages in vitro. Interaction with host cell lysosomes and host cell fate. Parasitology 80, 139–145.

    Article  PubMed  CAS  Google Scholar 

  • Montgomery, R., Webster, P. and Mellman, I. (1991). Accumulation of undigestible substances reduces fusion competence of macrophage lysosomes. J. Immunol. 147, 3087–3093.

    PubMed  CAS  Google Scholar 

  • Moreno, S.N.J., Silva, J., Vercesi, A.E. and Docampo, R. (1994). Cytosolic free calcium elevation in Trypanosoma cruzi is required for cell invasion. J. Exp. Med. 180, 1535 1540.

    Google Scholar 

  • Moskalewski, S. and Thyberg, J. (1990). Disorganization and reorganization of the Golgi complex and the lysosomal system in association with mitosis. J. Submicrosc. Cytol. Pathol. 22, 159–171.

    PubMed  CAS  Google Scholar 

  • Muniz, M., Alonso, M., Hidalgo, J. and Velasco, A. (1996). A regulatory role for cAMPdependent protein kinase in protein traffic along the exocytic route. J. Biol. Chem. 271, 30935–30941.

    Article  PubMed  CAS  Google Scholar 

  • Nogueira, N. and Cohn, Z. (1976). Trypanosoma cruzi: mechanism of entry and intracellular fate in mammalian cells. J. Exp. Med. 143, 1402–1420.

    Google Scholar 

  • Rodriguez, A., Martinez, I., Chung, A., Berlot, C.H. and Andrews, N.W. (1999). cAMP regulates Cat+-dependent exocytosis of lysosomes and lysosome-mediated cell invasion by trypanosomes. J. Biol. Chem. 274, 16754–16759.

    Google Scholar 

  • Rodriguez, A., Rioult, M.G., Ora, A. and Andrews, N.W. (1995). A trypanosome-soluble factor induces IP3 formation, intracellular Cat+ mobilization and microfilament rearrangement in host cells. J. Cell Biol. 129, 1263–1273.

    Article  PubMed  CAS  Google Scholar 

  • Rodriguez, A., Samoff, E., Rioult, M.G., Chung, A. and Andrews, N.W. (1996). Host cell invasion by trypanosomes requires lysosomes and microtubule/kinesin-mediated transport. J. Cell Biol. 134, 349–362.

    Article  PubMed  CAS  Google Scholar 

  • Rodriguez, A., Webster, P., Ortego, J. and Andrews, N.W. (1997). Lysosomes behave as Cat+-regulated exocytic vesicles in fibroblasts and epithelial cells. J. Cell Biol. in press.

    Google Scholar 

  • Ruiz, R.C., Favoreto, S., Dorta, M.L., Oshiro, M.E.M., Ferreira, A.T. and Manque, P.M. (1998). Infectivity of Trypanosoma cruzi strains is associated with differential expression of surface glycoproteins with differential Cat+ signaling activity. Biochem. J. 330, 505–511.

    PubMed  CAS  Google Scholar 

  • Schenkman, S., Andrews, N.W., Nussenzweig, V. and Robbins, E.S. (1988). Trypanosomacruzi invade a mammmalian epithelial cell in a polarized manner. Cell 55, 157–165.

    Google Scholar 

  • Schenkman, S., Jiang, M.S., Hart, G.W. and Nussenzweig, V. (1991). A novel cell surface trans-sialidase of Trypanosoma cruzi generates a stage-specific epitope required for invasion of mammalian cells. Cell 65, 1117–1125.

    Article  PubMed  CAS  Google Scholar 

  • Schenkman, S., Pontes, de, Carvalho, L and Nussenzweig, V. (1992). Trypanosoma cruzi trans-sialidase and neuraminidase activities can be mediated by the same enzymes. J. Exp. Med. 175, 567–75.

    Google Scholar 

  • Schenkman, S., Robbins, E.S. and Nussenzweig, V. (1991). Attachment of Trypanosoma cruzi to mammalian cells requires parasite energy, and invasion can be independent of the target cell cytoskeleton. Infect. Immun. 59, 645–654.

    PubMed  CAS  Google Scholar 

  • Silverstein, R.L. and Febbraio, M. (1992). Identification of lysosome-associated membrane protein-2 as an activation-dependent platelet surface glycoprotein. Blood 80, 1470 1475.

    Google Scholar 

  • Tapper, H. and Sundler, R. (1990). Role of lysosomal and cytosolic pH in the regulation of macrophage lysossomal enzyme secretion. Biochem. J. 272, 407–414.

    PubMed  CAS  Google Scholar 

  • Tardieux, I., Nathanson, M.H. and Andrews, N.W. (1994). Role in host cell invasion of Trypanosoma cruzi-induced cytosolic free Cat+ transients. J. Exp. Med. 179, 1017 1022.

    Google Scholar 

  • Tardieux, I., Webster, P., Ravesloot, J., Boron, W., Lunn, J.A., Henser, J.E. and Andrews, N.W. (1992). Lysosome recruitment and fusion are early events required for trypanosome invasion of mammalian cells. Cell 71, 1117–1130.

    Article  PubMed  CAS  Google Scholar 

  • Tomlinson, S., Vandekerckhove, F., Frevert, U. and Nussenzweig, V. (1995). The induction of Trypanosoma cruzi trypomastigote to amastigote transformation by low pH. Parasitology 110, 547–554.

    Article  PubMed  Google Scholar 

  • Yan, W. and Moreno, S.N. (1998). A method to assess invasion and intracellular replication of Trypanosoma cruzi based on differential uracil incorporation. J. Immunol. Meth. 220, 123–128.

    Article  CAS  Google Scholar 

  • Zhong, L., Lu, H.G., Moreno, S.N. and Docampo, R. (1998). Tyrosine phosphate hydrolysis of host proteins by Trypanosoma cruzi is linked to cell invasion. FEMS Microbiol. Lett. 161, 15–20.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, 02115, USA

    Barbara A. Burleigh

Authors
  1. Barbara A. Burleigh
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA

    Christian Tschudi

  2. Department of Microbiology and Immunology, Cornell University, Ithaca, New York, USA

    Edward J. Pearce

Rights and permissions

Reprints and permissions

Copyright information

© 2000 Springer Science+Business Media New York

About this chapter

Cite this chapter

Burleigh, B.A. (2000). Lysosome Exocytosis and Invasion of Non-Phagocytic Host Cells by Trypanosoma Cruzi . In: Tschudi, C., Pearce, E.J. (eds) Biology of Parasitism. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-4622-8_9

Download citation

  • DOI: https://doi.org/10.1007/978-1-4757-4622-8_9

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4419-4977-6

  • Online ISBN: 978-1-4757-4622-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation