Toxoplasma gondii down modulates cadherin expression in skeletal muscle cells inhibiting myogenesis
1 Laboratório de Biologia Estrutural, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, (Av. Brasil 4365), Rio de Janeiro (21040-361), Brazil
2 Laboratório Cultura de Células, Instituto de Biologia, Universidade do Estado do Rio de Janeiro, (Av. Prof. Manoel de Abreu 444), Rio de Janeiro (20550-170), Brazil
3 Laboratório de Genômica Funcional e Bioinformática, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, (Av. Brasil 4365), Rio de Janeiro (21040-361), Brazil
BMC Microbiology 2011, 11:110 doi:10.1186/1471-2180-11-110Published: 18 May 2011
Toxoplasma gondii belongs to a large and diverse group of obligate intracellular parasitic protozoa. Primary culture of mice skeletal muscle cells (SkMC) was employed as a model for experimental toxoplasmosis studies. The myogenesis of SkMC was reproduced in vitro and the ability of T. gondii tachyzoite forms to infect myoblasts and myotubes and its influence on SkMC myogenesis were analyzed.
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.