Toxoplasma gondii down modulates cadherin expression in skeletal muscle cells inhibiting myogenesis

In this study we show that, after 24 h of interaction, myoblasts (61%) were more infected with T. gondii than myotubes (38%) and inhibition of myogenesis was about 75%. The role of adhesion molecules such as cadherin in this event was investigated. First, we demonstrate that cadherin localization was restricted to the contact areas between myocytes/myocytes and myocytes/myotubes during the myogenesis process. Immunofluorescence and immunoblotting analysis of parasite-host cell interaction showed a 54% reduction in cadherin expression at 24 h of infection. Concomitantly, a reduction in M-cadherin mRNA levels was observed after 3 and 24 h of T. gondii-host cell interaction.These data suggest that T. gondii is able to down regulate M-cadherin expression, leading to molecular modifications in the host cell surface that interfere with membrane fusion and consequently affect the myogenesis process.Toxoplasma gondii is an obligatory intracellular parasite and an important human pathogen. Humans acquire toxoplasmosis due to oocyst seeding from cats, consumption of raw or undercooked meat or vertical transmission to the fetus during pregnancy. Studies of environmental factors in several communities indicated an important role for cultural and eating habits on this infection transmission [1]. During natural vertical infections, Toxoplasma initially crosses the intestinal epithelium of the mother, disseminates into the deep tissues and traverses the placenta, the blood-brain and the blood-retina barriers [2]. In both immunocompromised and immunocompetent individuals, Toxoplasma infection can cause a severe ocular pathology [3,4]. These parasites are able to invade and rapidly replicate in any nucleated host cell and may develop cysts, predominantly in neural and muscular tissues, initiating the chronic infection stage.Until now little attention has been given to skeletal muscle as a model in experimental toxoplasmosis studies [5-9], though skeletal muscle is one of the main si