| Grant number: | 04/03303-5 |
| Support Opportunities: | Research Projects - Thematic Grants |
| Start date: | October 01, 2004 |
| End date: | September 30, 2009 |
| Field of knowledge: | Biological Sciences - Biochemistry - Biochemistry of Microorganisms |
| Principal Investigator: | Maria Julia Manso Alves |
| Grantee: | Maria Julia Manso Alves |
| Host Institution: | Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil |
| City of the host institution: | São Paulo |
| Principal investigators | Walter Colli |
| Associated research 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)
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