A cardiomyocyte mannose receptor system is involved in Trypanosoma cruzi invasion and is down-modulated after infection

Mannosyl binding sites were detected "in vitro" on cardiomyocytes (CM) surf ace using horseradish peroxidase (HRP) as the ligand. Binding assays reveal ed a specific recognition system, which was time- and concentration-depende nt. The binding required physiological pH and was inhibited by EDTA and try psin treatments. HRP binding was reduced by pre-incubations with low concen trations of D-mannose. Ultrastructural analysis of the endocytic process wa s followed using HRP coupled to colloidal gold particles (HRP-Au). The trac er was found within caveolae characterizing early steps of the receptor-med iated endocytosis. The addition of 10 mM D-mannose to the interaction mediu m blocked Trypanosoma cruzi uptake by CM. The labeling of CM with a subsatu rating concentration of HRP-Au before their infection showed, by ultrastruc tural studies, that its association with trypomastigote forms occurred freq uently near to HRP-gold particles that could also be seen to comprise the p arasitophorous vacuole. After infection of CM with T. cruzi, a considerable reduction on HRP binding was noticed. Binding was almost completely restor ed by treating the infected cultures with the trypanocidal drug Nifurtimox. Our "in vitro" findings suggest that cardiomyocyte's mannose receptors loc alized at the sarcolemma mediates T. cruzi recognition and can be down-modu lated by parasite infection.