Phylloseptin-1 is Leishmanicidal for Amastigotes of Leishmania amazonensis Inside Infected Macrophages

Selma A. S. Kückelhaus, Daniela Sant’Ana de Aquino, Tatiana K. Borges, Daniel C. Moreira, Luciana de Magalhães Leite, Maria Imaculada Muniz-Junqueira, Carlos S. Kückelhaus, Gustavo A. Sierra Romero, Maura V. Prates, Carlos Bloch and José Roberto S. A. Leite
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Selma A. S. Kückelhaus: Núcleo de Pesquisa em Morfologia e Imunologia Aplicada, NuPMIA, Área de Morfologia, Faculdade de Medicina, FM, Universidade de Brasília, Brasília, DF 70910900, Brazil
Daniela Sant’Ana de Aquino: Núcleo de Pesquisa em Morfologia e Imunologia Aplicada, NuPMIA, Área de Morfologia, Faculdade de Medicina, FM, Universidade de Brasília, Brasília, DF 70910900, Brazil
Tatiana K. Borges: Laboratório de Imunologia Celular, Núcleo de Pesquisa em Morfologia e Imunologia Aplicada, NuPMIA, Faculdade de Medicina, FM, Universidade de Brasília, Brasília, DF 70910900, Brazil
Daniel C. Moreira: Núcleo de Pesquisa em Morfologia e Imunologia Aplicada, NuPMIA, Área de Morfologia, Faculdade de Medicina, FM, Universidade de Brasília, Brasília, DF 70910900, Brazil
Luciana de Magalhães Leite: Núcleo de Pesquisa em Morfologia e Imunologia Aplicada, NuPMIA, Área de Morfologia, Faculdade de Medicina, FM, Universidade de Brasília, Brasília, DF 70910900, Brazil
Maria Imaculada Muniz-Junqueira: Laboratório de Imunologia Celular, Núcleo de Pesquisa em Morfologia e Imunologia Aplicada, NuPMIA, Faculdade de Medicina, FM, Universidade de Brasília, Brasília, DF 70910900, Brazil
Carlos S. Kückelhaus: Laboratório de Imunologia Celular, Núcleo de Pesquisa em Morfologia e Imunologia Aplicada, NuPMIA, Faculdade de Medicina, FM, Universidade de Brasília, Brasília, DF 70910900, Brazil
Gustavo A. Sierra Romero: Laboratório de Leishmaniose, Núcleo de Medicina Tropical, Universidade de Brasília, Brasília, DF 70910900, Brazil
Maura V. Prates: Laboratório de Espectrometria de Massa, LEM, EMBRAPA Recursos Genéticos e Biotecnologia, Brasília, DF 70770900, Brazil
Carlos Bloch: Laboratório de Espectrometria de Massa, LEM, EMBRAPA Recursos Genéticos e Biotecnologia, Brasília, DF 70770900, Brazil
José Roberto S. A. Leite: Núcleo de Pesquisa em Morfologia e Imunologia Aplicada, NuPMIA, Área de Morfologia, Faculdade de Medicina, FM, Universidade de Brasília, Brasília, DF 70910900, Brazil

IJERPH, 2020, vol. 17, issue 13, 1-14

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.

Keywords: antimicrobial peptides; cytokine; leishmaniasis; oxidative stress (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2020
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