Peroxiredoxin expression restores infectivity in avirulent Trypanosoma cruzi strains: role of pathogen antioxidant enzymes as virulence factors

Chagas’ disease (CD), caused by the protozoan Trypanosoma cruzi , remains a major public health concern. During invasion, T. cruzi must deal with the oxidative environment found inside the mammalian host in order to spread and persist in the infected tissues for years. The parasite antioxidant armamentarium is critical for parasite survival either in cell (macrophage/cardiomyocyte) or animal models. In this work, we used a human isolated pathogenic T. cruzi clone (C8C3) that was maintained for years by regular mice passages preserving its virulence (C8C3hvir) or, in axenic culture, turning it avirulent (C8C3lvir). To study if the antioxidant armamentarium influences this virulence behaviour, we searched for the expression of different antioxidant enzymes. Specifically, we found that the virulent cell line expresses higher levels of mitochondrial (TcMPX) and cytosolic (TcCPX) peroxiredoxins (Prx) respect to the avirulent cell line. To determine if these changes in Prx expression may be involved in parasite virulence, we genetically-modified the avirulent cell line in order to overexpress TcCPX. Avirulent parasites overexpressing TcCPX restored infectivity to macrophages and cardiomyocytes in culture and, importantly, in the mouse model of CD.