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

Published online by Cambridge University Press:  22 September 2020

Patrícia de Almeida Machado
Affiliation:
Laboratório de Imunofarmacologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, RJ, Brazil Departamento de Parasitologia, Microbiologia e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Juiz de Fora, Juiz de Fora, MG, Brazil
Douglas Oliveira Escrivani
Affiliation:
Laboratório de Imunofarmacologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
Daniel Claudio Oliveira Gomes
Affiliation:
Núcleo de Doenças Infecciosas/Núcleo de Biotecnologia – Universidade Federal do Espírito Santo, Vitória, ES, Brazil
Bartira Rossi-Bergmann
Affiliation:
Laboratório de Imunofarmacologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
Suzana Passos Chaves
Affiliation:
Laboratório de Imunoparasitologia, Universidade Federal do Rio de Janeiro Campus Macaé, RJ, Brazil
Elaine Soares Coimbra*
Affiliation:
Departamento de Parasitologia, Microbiologia e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Juiz de Fora, Juiz de Fora, MG, Brazil
Herbert Leonel de Matos Guedes*
Affiliation:
Laboratório de Imunofarmacologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, RJ, Brazil UFRJ Campus Duque de Caxias Professor Geraldo Cidade – Universidade Federal do Rio de Janeiro, Duque de Caxias, Rio de Janeiro, RJ, Brazil
*
Author for correspondence: Elaine Soares Coimbra, E-mail: elaine.coimbra@ufjf.edu.br, Herbert Leonel de Matos Guedes, E-mail: herbert@biof.ufrj.br, herbert@ioc.fiocruz.br
Author for correspondence: Elaine Soares Coimbra, E-mail: elaine.coimbra@ufjf.edu.br, Herbert Leonel de Matos Guedes, E-mail: herbert@biof.ufrj.br, herbert@ioc.fiocruz.br

Abstract

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.

Type
Research Article
Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

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