AUTHOR=Vaitkevicius-Antão Victor , Moreira-Silva Jady , Reino Isabelle Barreto da Silva Moreira , Melo Maria Gabriella Nunes de , Silva-Júnior José Noé da , Andrade Alexsandra Frazão de , Araújo Paulo Sérgio Ramos de , Bezerra Raquel Pedrosa , Marques Daniela de Araújo Viana , Ferreira Silvana , Pessoa-e-Silva Rômulo , Lorena Virginia Maria Barros de , Paiva-Cavalcanti Milena de 

TITLE=Therapeutic Potential of Photosynthetic Microorganisms for Visceral Leishmaniasis: An Immunological Analysis

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.891495

DOI=10.3389/fimmu.2022.891495

ISSN=1664-3224

ABSTRACT=<p>New therapeutic strategies for visceral leishmaniasis (VL) have been studied, and the development of an immunotherapeutic agent that modulates the host’s immune response is necessary. The aim of this study was to evaluate <italic>in vitro</italic> the bioactive extracts of photosynthetic microorganisms (PMs) for their leishmanicidal/leishmanistatic and immunomodulatory potentials. Bioactive extracts from PMs (<italic>Arthrospira platensis</italic> and <italic>Dunaliella tertiolecta</italic>) were obtained by sonication. Reference drugs, miltefosine (MTF) and N-methylglucamine antimoniate (Sb<sup>V</sup>), were also evaluated. The selectivity index (SI) of treatments was determined by assays of inhibitory concentration (IC<sub>50</sub>) in <italic>Leishmania infantum</italic> cells and cytotoxic concentrations (CC<sub>50</sub>) in human peripheral blood mononuclear cells by the MTT method. The immune response was evaluated in healthy human cells by the production of cytokines and nitric oxide (NO) and the gene expression of <italic>Tbx21</italic>, <italic>GATA3</italic>, <italic>RORc</italic>, and <italic>FOXP3</italic>, using four concentrations (CC<sub>50</sub>, ½ CC<sub>50</sub>, ¼ CC<sub>50</sub>, and IC<sub>50</sub>) for <italic>in-vitro</italic> stimulation. Based on the data obtained, we observed that the extracts of <italic>D. tertiolecta</italic> (SI = 4.7) and <italic>A. platensis</italic> (SI = 3.8) presented better results when compared to Sb<sup>V</sup> (SI = 2.1). When analyzing the immune response results, we identified that the extracts of PMs stimulated the production of cytokines of the Th1 profile more than the reference drugs. The extracts also demonstrated the ability to stimulate NO synthesis. Regarding gene expression, in all concentrations of <italic>A. platensis</italic> extracts, we found a balance between the Th1/Th2 profile, with the average expression of the <italic>Tbx21</italic> gene more than the <italic>GATA3</italic> in the highest concentration (CC<sub>50</sub>). Regarding the extract of <italic>D. tertiolecta</italic>, we can observe that, in the lowest concentrations, a balance between all the genes was present, with the average expression of the <italic>GATA3</italic> gene being lower than the others. The best result was found in the ½ CC<sub>50</sub> concentration, stimulating a balanced positive expression between the Th1×Th17×Treg profiles, with a negative expression of <italic>GATA3</italic>. Thus, PM extracts showed promising results, presenting low toxicity, leishmanicidal/leishmanistatic activity, and induction of the immune response, which could be potential therapeutic candidates for VL.</p>