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Trypanosoma cruzi P21 protein exacerbates Leishmania (L.) amazonensis infection
Thaise Lara Teixeira1, Samuel Cota Teixeira1, Bruna Cristina Borges1
1Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Uberlândia, Minas Gerais, Brazil.
Abstract:
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.
Insights
The recombinant protein rP21, effective against Trypanosoma cruzi, unexpectedly worsened Leishmania amazonensis infections in mice. This study highlights rP21
Area of Science:
- Parasitology
- Immunology
- Drug Discovery
Background:
- Chagas disease, caused by Trypanosoma cruzi, affects millions globally, with limited treatment options.
- A T. cruzi-derived recombinant protein (rP21) shows promise in modulating immunity and controlling T. cruzi infections.
- The therapeutic potential of rP21 against other trypanosomatids, like Leishmania, is unknown.
Purpose of the Study:
- To evaluate the efficacy of rP21 as a therapeutic agent against Leishmania (L.) amazonensis infection.
- To determine if rP21's immunomodulatory effects extend to Leishmania infections.
- To assess the impact of rP21 treatment on parasite load and host immune response in a murine model of leishmaniasis.
Main Methods:
- A murine model of Leishmania (L.) amazonensis infection was established in BALB/c mice.
- Infected mice were treated with the recombinant protein rP21.
- Parasite load, lesion size, and inflammatory infiltrate in paw tissues were quantified.
Main Results:
- rP21 treatment did not improve, but rather exacerbated, L. (L.) amazonensis infection.
- Increased parasite burdens and larger lesion sizes were observed in rP21-treated mice.
- rP21 administration led to intensified inflammatory responses in the infected paw tissues.
Conclusions:
- The recombinant protein rP21 is not a suitable therapeutic candidate for Leishmania (L.) amazonensis infection.
- rP21 may potentially worsen the disease progression in leishmaniasis.
- Further research is needed to understand the differential effects of rP21 on distinct trypanosomatid infections.
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