Trypanosoma cruzi P21 protein exacerbates Leishmania (L.) amazonensis infection

The protozoan parasite Trypanosoma cruzi, the etiological agent of Chagas disease, affects millions of people worldwide. Current treatments rely on drugs effective only in the acute phase, making the search for new therapeutic targets a priority. While a recombinant protein based on T. cruzi P21 (rP21) exhibits immunomodulatory properties and contributes to controlling parasitism and inflammation during T. cruzi infection, its efficacy against other trypanosomatids remains unexplored. This study investigated the impact of rP21 on Leishmania (L.) amazonensis infection in a murine model. Contrary to our expectations, treatment with rP21 did not ameliorate L. (L.) amazonensis infection. Instead, rP21 treatment resulted in increased parasite load in the paws of infected BALB/c mice, evidenced by larger lesion sizes and higher parasite burdens, accompanied by an intensified inflammatory infiltrate in the paw tissue. These findings suggest that despite its promising effects in the context of T. cruzi infection, rP21 may not be a suitable therapeutic candidate for L. amazonensis infection and might even exacerbate disease.