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Involvement of host cell heparan sulfate proteoglycan in Trypanosoma cruzi amastigote attachment and invasion

Published online by Cambridge University Press:  27 January 2011

R. BAMBINO-MEDEIROS
Affiliation:
Laboratório de Ultra-estrutura Celular, Instituto Oswaldo Cruz/FIOCRUZ, Av. Brasil 4365, Manguinhos, Rio de Janeiro, RJ, 21045-900, Brazil
F. O. R. OLIVEIRA Jr
Affiliation:
Laboratório de Ultra-estrutura Celular, Instituto Oswaldo Cruz/FIOCRUZ, Av. Brasil 4365, Manguinhos, Rio de Janeiro, RJ, 21045-900, Brazil
C. M. CALVET
Affiliation:
Laboratório de Ultra-estrutura Celular, Instituto Oswaldo Cruz/FIOCRUZ, Av. Brasil 4365, Manguinhos, Rio de Janeiro, RJ, 21045-900, Brazil
D. VICENTE
Affiliation:
Laboratório de Ultra-estrutura Celular, Instituto Oswaldo Cruz/FIOCRUZ, Av. Brasil 4365, Manguinhos, Rio de Janeiro, RJ, 21045-900, Brazil
L. TOMA
Affiliation:
Departamento de Bioquímica Universidade Federal de São Paulo, UNIFESP, SP, Rua Tres de Maio, 100 Vila Clementino - São Paulo, SP, 04044-020, Brazil
M. A. KRIEGER
Affiliation:
Instituto Carlos Chagas, Instituto de Biologia Molecular do Paraná/FIOCRUZ, Rua Professor Algacyr Munhoz Mader 3775, Curitiba, PR, 81350-010, Brazil
M. N. MEIRELLES
Affiliation:
Laboratório de Ultra-estrutura Celular, Instituto Oswaldo Cruz/FIOCRUZ, Av. Brasil 4365, Manguinhos, Rio de Janeiro, RJ, 21045-900, Brazil
M. C. S. PEREIRA*
Affiliation:
Laboratório de Ultra-estrutura Celular, Instituto Oswaldo Cruz/FIOCRUZ, Av. Brasil 4365, Manguinhos, Rio de Janeiro, RJ, 21045-900, Brazil
*
*Corresponding author: Laboratório de Ultra-estrutura Celular, Instituto Oswaldo Cruz, FIOCRUZ, Av. Brasil 4365, Manguinhos, 21045-900 Rio de Janeiro, RJ, Brazil. Tel: +5521 25984330; Fax: +5521 22604434. E-mail: mirian@ioc.fiocruz.br

Summary

Cell surface glycosaminoglycans (GAGs) play an important role in the attachment and invasion process of a variety of intracellular pathogens. We have previously demonstrated that heparan sulfate proteoglycans (HSPG) mediate the invasion of trypomastigote forms of Trypanosoma cruzi in cardiomyocytes. Herein, we analysed whether GAGs are also implicated in amastigote invasion. Competition assays with soluble GAGs revealed that treatment of T. cruzi amastigotes with heparin and heparan sulfate leads to a reduction in the infection ratio, achieving 82% and 65% inhibition of invasion, respectively. Other sulfated GAGs, such as chondroitin sulfate, dermatan sulfate and keratan sulfate, had no effect on the invasion process. In addition, a significant decrease in infection occurred after interaction of amastigotes with GAG-deficient Chinese Hamster Ovary (CHO) cells, decreasing from 20% and 28% in wild-type CHO cells to 5% and 9% in the mutant cells after 2 h and 4 h of infection, respectively. These findings suggest that amastigote invasion also involves host cell surface heparan sulfate proteoglycans. The knowledge of the mechanism triggered by heparan sulfate-binding T. cruzi proteins may provide new potential candidates for Chagas disease therapy.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2011

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