Benznidazole (Bz) is the recommended drug for the treatment of Chagas disease; however, its efficacy may vary according to the sensitivity of Trypanosoma cruzi strains to the drug and host immune background. The study evaluated the immune response of peripheral blood mononuclear cells (PBMC) that were infected in vitro with the Colombian strain (Col) and treated with Bz. The co‐cultures were incubated for 24 h, 5 and 10 days, where cytokine dosage was performed in the supernatant and evaluation of the cells for CD28+ and CTLA‐4+ molecules in CD4+ and CD8+ lymphocytes, and CD80+, CD86+ and HLA‐DR+ in CD14+ cells. The results showed that Col induced a strong inflammatory response, with an increase in IFN‐γ and TNF early in the infection (24 h), however, from 5 days of infection on, TNF production declined, and IL‐10 production increased, which may be associated with a control mechanism of the exacerbated inflammatory response. The Bz treatment did not significantly alter the frequencies of the phenotypes evaluated both T cell subsets and CD14+ cells. Therefore, this study reinforces the need for typing the patient's strain to guide therapy and promote individualized treatment protocols due to the heterogeneous genetic background among T. cruzi strains.
Due to the limitations of Chagas disease therapy, microalgae can be promising in the search of new trypanocidal compounds, since these organisms produce bioactive compounds with large pharmaceutical applications, including antiparasitic effects. In this work, trypanocidal activity of aqueous extract of Tetradesmus obliquus and, for the first time, aqueous extract of Chlorella vulgaris, were evaluated against trypomastigote forms of Trypanosoma cruzi. In addition, cytotoxic activity employing Vero cells was evaluated. Our results showed that C. vulgaris and T. obliquus present trypanocidal activity (IC50 = 32.9 µg ml -1 and 36.4 µg ml -1 , respectively), however, C. vulgaris did not present cytotoxic effects in Vero cells (CC50 > 600 µg ml -1 ) and displayed a higher selectivity against trypomastigotes forms of T. cruzi (SI > 18). Thus, microalgae extracts, particularly the aqueous extract of C. vulgaris, are promising potential candidates for the development of natural antichagasic drugs.
Trypanosoma cruzi causes the lethal Chagas disease, which is endemic in Latin America. Flowers of Moringa oleifera (Moringaceae) express a trypsin inhibitor (MoFTI) whose toxicity to T. cruzi trypomastigotes was previously reported. Here, we studied the effects of MoFTI on the viability of human peripheral blood mononuclear cells (PBMCs) as well as on the production of cytokines and nitric oxide (NO) by T. cruzi-infected PBMCs. Incubation with MoFTI (trypsin inhibitory activity: 62 U/mg) led to lysis of trypomastigotes (LC50 of 43.5 µg/mL) but did not affect the viability of PBMCs when tested at concentrations up to 500 µg/mL. A selectivity index > 11.48 was determined. When T. cruzi-infected PBMCs were treated with MoFTI (43.5 or 87.0 µg/mL), the release of the pro-inflammatory cytokine TNF-α and INF-γ, as well as of NO, was stimulated. The release of the anti-inflammatory cytokine IL-10 also increased. In conclusion, the toxicity to T. cruzi and the production of IL-10 by infected PBMCs treated with MoFTI suggest that this molecule may be able to control parasitemia while regulating the inflammation, preventing the progress of Chagas disease. The data reported here stimulate future investigations concerning the in vivo effects of MoFTI on immune response in Chagas disease.
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