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Behavior of two Leishmania infantum strains—evaluation of susceptibility to antimonials and expression of microRNAs in experimentally infected J774 macrophages and in BALB/c mice

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Abstract

Strains of the same Leishmania parasite species, isolated from different host organisms, may exhibit unique infection profiles and induce a change in the expression of microRNAs among host macrophages and in model host mice. MicroRNAs (MiR) are endogenous molecules of about 22 nucleotides that are involved in many regulatory processes, including the vertebrate host immune response. In this respect, the infectivity and susceptibility to antimonials of two L. infantum strains, BH46, isolated from human, and OP46, isolated from symptomatic dog, were characterized in J774 macrophages and BALB/c mice. Parasite burden was assessed in the liver, spleen, and bone marrow using the serial limiting dilution technique. A higher parasite burden was observed in the spleen and bone marrow of animals infected with OP46 compared to BH46 strain. Our results also showed that OP46 was less susceptible to the antimonials. In addition, miR-122 and miR-155 expression was evaluated in the liver and J774 macrophages, and in spleens from infected animals, respectively. An increase was observed in the expression of miR-155 in J774 macrophages infected with both strains compared to uninfected cells, with a higher expression in cells infected with OP46. However, no difference in the expression of miR-122 and miR-155 was observed in the infected animals. Thus, this study shows that OP46 was more infective for mice, it caused a higher increase in miR-155 expression in infected macrophages and was less susceptible to the antimonials evaluated. These data suggest that alteration in miR-155 level likely plays a role in regulating the response to L. infantum.

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Acknowledgements

We thank the assistance provided by Dr. Rodrigo Pedro Pinto Soares from Centro de Pesquisa René Rachou (FIOCRUZ, Minas Gerais, Brazil) and Dr. Alexandre Barbosa Reis from the Laboratório de Imunopatologia at NUPEB/UFOP. We thank also the Centro de Ciência Animal-CCA/UFOP for the animals, Dra. Angélica Lima for allowing the use of the Laboratório de Bioquímica e Imunologia Clínicas and Laboratório Piloto de Análises Clínicas (LAPAC/UFOP) and Dr. Frederic Frezard from Federal University of Minas Gerais for kindly supplying the meglumine antimoniate. Thanks also to the graduate student Douglas Dophine from the Laboratory of Clinical Research at CiPHARMA/UFOP for the help with sheet reading.

Funding

The CNPq, FAPEMIG, and Rede Mineira de Bioterismo financially supported this study. This work was supported by the Federal University of Ouro Preto (UFOP), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Laboratório de Pesquisas Clínicas, Programa de Pós-Graduação em Ciências Farmacêuticas (CiPHARMA), Escola de Farmácia, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, 35400-000, Brazil

    Stella Costa Silva, Débora Faria Silva, Tamires Cunha Almeida, Glenda Nicioli da Silva & Simone Aparecida Rezende

  2. Laboratório de Fitotecnologia, Programa de Pós-Graduação em Ciências Farmacêuticas (CiPHARMA), Escola de Farmácia, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil

    Fernanda Barçante Perasoli

  3. Laboratório de Imunobiologia da Inflamação, Programa de Pós-Graduação em Ciências Biológicas, Departamento de Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil

    André Talvani Pedrosa da Silva

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  1. Stella Costa Silva
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Correspondence to Simone Aparecida Rezende.

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The procedures adopted in this study were in accordance with the National Council on Animal Experiments and Control (CONCEA-MCT Brazil) guidelines and approved by the Ethics Committee on the Use of Animals of the Federal University of Ouro Preto, under protocol number 2015/49.

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Silva, S.C., Silva, D.F., Almeida, T.C. et al. Behavior of two Leishmania infantum strains—evaluation of susceptibility to antimonials and expression of microRNAs in experimentally infected J774 macrophages and in BALB/c mice. Parasitol Res 117, 2881–2893 (2018). https://doi.org/10.1007/s00436-018-5979-3

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