Abstract
Leishmania protozoans are the causal agents of neglected diseases that represent an important public health issue worldwide. The growing occurrence of drug-resistant strains of Leishmania and severe side effects of available treatments represent an important challenge for the leishmaniases treatment. We have previously reported the leishmanicidal activity of phylloseptin-1 (PSN-1), a peptide found in the skin secretion of Phyllomedusa azurea (=Pithecopus azureus), against Leishmania amazonensis promastigotes. However, its impact on the amastigote form of L. amazonensis and its impact on infected macrophages are unknown. In this work, we evaluated the effects of PSN-1 on amastigotes of L. amazonensis inside macrophages infected in vitro. We assessed the production of hydrogen peroxide and nitric oxide, as well as the levels of inflammatory and immunomodulatory markers (TGF-β, TNF-α and IL-12), in infected and non-infected macrophages treated with PSN-1. Treatment with PSN-1 decreased the number of infected cells and the number of ingested amastigotes per cell when compared with the untreated cells. At 32 µM (64 µg/mL), PSN-1 reduced hydrogen peroxide levels in both infected and uninfected macrophages, whereas it had little effect on NO production or TGF-β release. The effect of PSN-1 on IL-12 and TNF-α secretion depended on its concentration, but, in general, their levels tended to increase as PSN-1 concentration increased. Further in vitro and in vivo studies are needed to clarify the mechanisms of action of PSN-1 and its interaction with the immune system aiming to develop pharmacological applications.
Highlights
Protozoans of the Leishmania genus are the causal agents of important but neglected tropical diseases that affect 0.7–1 million people each year worldwide [1,2,3,4]
In the case of leishmaniasis, we have previously reported that phylloseptin-1 (PSN-1), formerly known as PS-1 [16], has a strong activity against
Incubation of amastigote-infected macrophages with different concentrations of PSN-1 decreased the percentage of infected cells in a dose-dependent manner compared with the untreated control culture (Figure 2a,d)
Summary
Protozoans of the Leishmania genus are the causal agents of important but neglected tropical diseases that affect 0.7–1 million people each year worldwide [1,2,3,4]. Leishmaniases are classified as cutaneous, mucosal and visceral, depending on the clinical manifestations. Res. Public Health 2020, 17, 4856; doi:10.3390/ijerph17134856 www.mdpi.com/journal/ijerph
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