Involvement of host cell heparan sulfate proteoglycan in Trypanosoma cruzi amastigote attachment and invasion.
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.
Laboratório de Ultra-estrutura Celular, Instituto Oswaldo Cruz/FIOCRUZ, Av Brasil 4365, Manguinhos, Rio de Janeiro 21045-900, Brazil. mirian@ioc.fiocruz.br
R
R
Bambino-Medeiros
F O R
FO
Oliveira
C M
CM
Calvet
D
D
Vicente
L
L
Toma
M A
MA
Krieger
M N
MN
Meirelles
M C S
MC
Pereira
D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D014355:Chagas Disease / Q000469:parasitology*; D006224:Cricetinae; D003412:Cricetulus; D005434:Flow Cytometry; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D006493:Heparin / Q000494:pharmacology*; D006497:Heparan Sulfate / Q000494:pharmacology*; D006790:Host-Parasite Interactions / Q000187:drug effects; D051379:Mice; D046529:Microscopy, Electron, Transmission; D009154:Mutation; D032383:Myocytes, Cardiac / Q000469:parasitology; D013997:Time Factors; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000472:pathogenicity / Q000502:physiology*
D019812:Heparan Sulfate Proteoglycans; D006493:Heparin; D006497:Heparan Sulfate