Estudo in vitro do potencial leishmanicida e imunomodulador da lectina da alga marinha Solieria filiformis contra Leishmania infantum

Abstract

Lectins are proteins capable of specifically and reversibly binding to carbohydrates, playing important roles in the modulation of the immune response. The immunomodulatory effect of these molecules has been extensively studied, particularly for their potential application in the treatment of parasites, including the etiological agents of leishmaniasis. In Brazil, visceral leishmaniasis (VL), caused by the protozoan Leishmania infantum, is a serious disease with high lethality. Its treatment is primarily based on the use of meglumine antimoniate and amphotericin B. However, this treatment has presented several problems, such as discontinuation, adverse effects, and the emergence of resistant strains. Therefore, there is a need to search for new molecules capable of controlling and treating VL, such as lectins from marine algae. In this context, the objective was to investigate the in vitro leishmanicidal and immunomodulatory potential of the lectin from the red marine alga Solieria filiformis (LSf) against L. infantum. To assess the leishmanicidal activity against amastigotes, macrophages from the J774 cell line were infected with L. infantum promastigotes (107 parasites/mL) and treated with Glucantime® (2 mg/mL; positive control) or LSf (5, 10, 25, 50, and 100 μg/mL) for 24 and 48 hours. In evaluating the mechanism of action of LSf, the levels of nitric oxide (NO) and several pro-inflammatory (TNF-α and IL-12) and anti-inflammatory (IL-4 and IL-10) cytokines were measured. The results were expressed as the mean ± standard error of the mean, with significance considered at p<0.05 (ANOVA; Tukey's test). The results showed that LSf significantly reduced the parasitic load in macrophages infected with amastigotes, surpassing the reduction in the positive control. Its mechanism of action is related to increased nitrosative stress through the cytokines TNF-α and IL-12. Additionally, LSf induced the production of the cytokine IL-10, demonstrating its ability to modulate the inflammatory response. These results highlight the promising potential of Solieria filiformis lectins for the development of new drugs aimed at the treatment of visceral leishmaniasis.