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Interaction between Trypanosoma cruzi and host: binders, receptors and conditioners of intracellular development

Grant number: 04/03303-5
Support type:Research Projects - Thematic Grants
Duration: October 01, 2004 - September 30, 2009
Field of knowledge:Biological Sciences - Biochemistry - Biochemistry of Microorganisms
Principal Investigator:Maria Julia Manso Alves
Grantee:Maria Julia Manso Alves
Home Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Co-Principal Investigators:Walter Colli
Associated grant(s):05/58377-6 - Trypanosoma Cruzi shed vesicles enhance host cell invasion by exploring toll-like receptor 2 activation, AR.BR

Abstract

The acute phase of Chagas Disease presents a generalized infection, with Trypanosoma cruzi present in almost all the organs and in the interior of different types of cell: smooth, skeletal and cardiac muscle fibers, fibroblasts, endothelial, glial, Schwann cells, neurons, macrophages and adipocytes. The peripheral nervous system is compromised, as, for example, in the alterations that occur in the digestive tract (megacolon and megaesophagus), attributed to the destruction of nerve cells of the enteric autonomous nervous system, including the plexus of Meisser and Auerbach, but rarely is the central nervous system compromised, except in immunosuppressed patients and children of young age. The invasion (in the real sense) and the intracellular survival of T.cruzi in the vertebrate host are two essential stages for the success of the infection in a particular cell. Our Laboratory has dedicated itself to characterizing a family of proteins (Tc-85) involved in the adhesion of the parasite to epithelial cells and to laminin. However, of the 30 members cloned (belonging to two different subfamilies), only 25 per cent display the bonding sequence of laminin, recently mapped. We have evidence, still preliminary, that the members of this family also bond to other elements of the extracellular matrix. What could be, then, the bonding sequences of other elements of the matrix? What could be the other receptors, including those located in the membranes of the host cells? One of the points of interest is to verify if molecules of two sub-families of the Tc-85 family bond with different cell types and is there could be specific sequences for each receptor. We also do not know if there is a response from the host cell in the face of these bonders. In addition, one of the points we consider fundamental at present is to verify if the conclusions of the studies of adhesion in vitro would correspond in vivo. On the other hand, we do not know how many members of the Tc-85 family are simultaneously expressed by parasite, admitting that there is variation of individual expression, suggested by some data in the literature. (AU)

Articles published in Pesquisa FAPESP Magazine about the research grant:
Parasite poised for the attack 

Scientific publications (7)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
TONELLI, R. R.; TORRECILHAS, A. C.; JACYSYN, J. F.; JULIANO, M. A.; COLLI, W.; ALVES, M. J. M. In vivo infection by Trypanosoma cruzi: The conserved FLY domain of the gp85/trans-sialidase family potentiates host infection. Parasitology, v. 138, n. 4, p. 481-492, APR 2011. Web of Science Citations: 10.
TONELLI, RENATA R.; GIORDANO, RICARDO J.; BARBU, ELENA MAGDA; TORRECILHAS, ANA CLAUDIA; KOBAYASHI, GERSON S.; LANGLEY, ROBERT R.; ARAP, WADIH; PASQUALINI, RENATA; COLLI, WALTER; ALVES, MARIA JULIA M. Role of the gp85/Trans-Sialidases in Trypanosoma cruzi Tissue Tropism: Preferential Binding of a Conserved Peptide Motif to the Vasculature In Vivo. PLoS Neglected Tropical Diseases, v. 4, n. 11, p. e864, 2010. Web of Science Citations: 28.
SILBER, ARIEL M.; TONELLI, RNATA R.; LOPES, CAMILA G.; CUNHA-E-SILVA, NARCISA; TORRECILHAS, ANA CLAUDIA T.; SCHUMACHER, ROBERT I.; COLLI, WALTER; ALVES, MARIA JULIA M. Glucose uptake in the mammalian stages of Trypanosoma cruzi. Molecular and Biochemical Parasitology, v. 168, n. 1, p. 102-108, NOV 2009. Web of Science Citations: 34.
TROCOLI TORRECILHAS, ANA CLAUDIA; TONELLI, RENATA ROSITO; PAVANELLI, WANDER ROGERIO; DA SILVA, JOAO SANTANA; SCHUMACHER, ROBERT IVAN; DE SOUZA, WANDERLEY; CUNHA E SILVA, NARCISA; ABRAHAMSOHN, ISES DE ALMEIDA; COLLI, WALTER; MANSO ALVES, MARIA JULIA. Trypanosoma cruzi: parasite shed vesicles increase heart parasitism and generate an intense inflammatory response. Microbes and Infection, v. 11, n. 1, p. 29-39, JAN 2009. Web of Science Citations: 84.
MAGDESIAN, MARGARET H.; TONELLI, RENATA R.; FESSEL, MELISSA R.; SILVEIRA, MARIANA S.; SCHUMACHER, ROBERT I.; LINDEN, RAFAEL; COLLI, WALTER; ALVES, MARIA JÚLIA M. A conserved domain of the gp85/trans-sialidase family activates host cell extracellular signal-regulated kinase and facilitates Tzypanosoma cruzi infection. Experimental Cell Research, v. 313, n. 1, p. 210-218, Jan. 2007.
SILBER, ARIEL M.; GALVEZ ROJAS, ROBERT L.; URIAS, URSULA; COLLI, WALTER; ALVES, MARIA JÚLIA MANSO. Biochemical characterization of the glutamate transport in Trypanosoma cruzi. International Journal for Parasitology, v. 36, n. 2, p. 157-163, Feb. 2006.
CANEPA‚ G.E.; BOUVIER‚ L.A.; URIAS‚ U.; MIRANDA‚ M.R.; COLLI‚ W.; ALVES‚ M.J.M.; PEREIRA‚ C.A. Aspartate transport and metabolism in the protozoan parasite Trypanosoma cruzi. FEMS Microbiology Letters, v. 247, n. 1, p. 65-71, 2005.

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