Vitamin D increases killing of intracellular Leishmania amazonensis in vitro independently of macrophage oxidative mechanisms

TY - JOUR

T1 - Vitamin D increases killing of intracellular Leishmania amazonensis in vitro independently of macrophage oxidative mechanisms

AU - de Almeida MacHado, Patrícia

AU - Oliveira Escrivani, Douglas

AU - Oliveira Gomes, Daniel Claudio

AU - Rossi-Bergmann, Bartira

AU - Passos Chaves, Suzana

AU - Soares Coimbra, Elaine

AU - de Matos Guedes, Herbert Leonel

N1 - Funding Information: This study was funded by Programa Jovem Cientista do Nosso Estado (FAPERJ - E-26/203.215/2015); Productivity Fellowships from CNPq (304712/2016-7), FAPERJ (E-26/202-422/2017) and the Agency for Support and Evaluation of Graduate Education (CAPES) Finance code 001. Publisher Copyright: © 2020 Cambridge University Press. All rights reserved. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020/12

Y1 - 2020/12

N2 - Vitamin D has been reported to activate macrophage microbicidal mechanisms by inducing the production of antimicrobial peptides and nitric oxide (NO), but conversely has been shown to contribute to a greater susceptibility to Leishmania amazonensis infection in mice. Thus, this study aimed to evaluate the role of vitamin D during intracellular infection with L. amazonensis by examining its effect on macrophage oxidative mechanisms and parasite survival in vitro. Vitamins D2 and D3 significantly inhibited promastigote and amastigote growth in vitro. Vitamin D3 was not able to induce NO and reactive oxygen species (ROS) production in uninfected macrophages or macrophages infected with L. amazonensis. In addition, vitamin D3 in combination with interferon (IFN)-γ did not enhance amastigote killing and in fact, significantly reduced NO and ROS production when compared with the effect of IFN-γ alone. In this study, we demonstrated that vitamin D directly reduces parasite growth in infected macrophages (approximately 50-60% at 50 μm) but this effect is independent of the activation of macrophage oxidative mechanisms. These findings will contribute to a better understanding of the role of vitamin D in cutaneous leishmaniasis.

AB - Vitamin D has been reported to activate macrophage microbicidal mechanisms by inducing the production of antimicrobial peptides and nitric oxide (NO), but conversely has been shown to contribute to a greater susceptibility to Leishmania amazonensis infection in mice. Thus, this study aimed to evaluate the role of vitamin D during intracellular infection with L. amazonensis by examining its effect on macrophage oxidative mechanisms and parasite survival in vitro. Vitamins D2 and D3 significantly inhibited promastigote and amastigote growth in vitro. Vitamin D3 was not able to induce NO and reactive oxygen species (ROS) production in uninfected macrophages or macrophages infected with L. amazonensis. In addition, vitamin D3 in combination with interferon (IFN)-γ did not enhance amastigote killing and in fact, significantly reduced NO and ROS production when compared with the effect of IFN-γ alone. In this study, we demonstrated that vitamin D directly reduces parasite growth in infected macrophages (approximately 50-60% at 50 μm) but this effect is independent of the activation of macrophage oxidative mechanisms. These findings will contribute to a better understanding of the role of vitamin D in cutaneous leishmaniasis.

KW - Leishmania amazonensis

KW - macrophages

KW - NO

KW - ROS

KW - Vitamin D

UR - https://www.scopus.com/pages/publications/85096343780

U2 - 10.1017/S0031182020001791

DO - 10.1017/S0031182020001791

M3 - Article

C2 - 32958098

AN - SCOPUS:85096343780

SN - 0031-1820

VL - 147

SP - 1792

EP - 1800

JO - Parasitology

JF - Parasitology

IS - 14

ER -