Leishmania amazonensis impairs DC function by inhibiting CD40 expression via A2B adenosine receptor activation

Authors

  • Amanda B. Figueiredo,

    1. Laboratório de Imunoparasitologia, Departamento de Ciências Biológicas, ICEB/NUPEB, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil
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  • Tiago D. Serafim,

    1. Laboratório de Imunoparasitologia, Departamento de Ciências Biológicas, ICEB/NUPEB, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil
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  • Eduardo A. Marques-da-Silva,

    Corresponding author
    1. Laboratório de Imunoparasitologia, Departamento de Ciências Biológicas, ICEB/NUPEB, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil
    • Correspondence: Dr. Luís Carlos Crocco Afonso, Laboratório de Imunoparasitologia, Departamento de Ciências Biológicas, ICEB/NUPEB, Universidade Federal de Ouro Preto, Campus do Morro do Cruzeiro, 35400–000 Ouro Preto, Minas Gerais, Brazil Fax: +55-31-3559-1680 e-mail: afonso@nupeb.ufop.br

      Current address: Dr. Eduardo A. Marques-da-Silva, Laboratório de Imunovirologia Molecular, Departamento de Biologia Geral, CCB, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil

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  • José R. Meyer-Fernandes,

    1. Laboratório de Bioquímica Celular, Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
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  • and Luís C. C. Afonso

    Corresponding author
    1. Laboratório de Imunoparasitologia, Departamento de Ciências Biológicas, ICEB/NUPEB, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil
    • Correspondence: Dr. Luís Carlos Crocco Afonso, Laboratório de Imunoparasitologia, Departamento de Ciências Biológicas, ICEB/NUPEB, Universidade Federal de Ouro Preto, Campus do Morro do Cruzeiro, 35400–000 Ouro Preto, Minas Gerais, Brazil Fax: +55-31-3559-1680 e-mail: afonso@nupeb.ufop.br

      Current address: Dr. Eduardo A. Marques-da-Silva, Laboratório de Imunovirologia Molecular, Departamento de Biologia Geral, CCB, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil

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Abstract

Dendritic cells (DCs) play an essential role in the modulation of immune responses and several studies have evaluated the interactions between Leishmania parasites and DCs. While extracellular ATP exhibits proinflammatory properties, adenosine is an important anti-inflammatory mediator. Here we investigated the effects of Leishmania infection on DC responses and the participation of purinergic signalling in this process. Bone marrow-derived dendritic cells (BMDCs) from C57BL/6J mice infected with Leishmania amazonensis, Leishmania braziliensis or Leishmania major metacyclic promastigotes showed decreased major histocompatibility complex (MHC) class II and CD86 expression and increased ectonucleotidase expression as compared with uninfected cells. In addition, L. amazonensis-infected DCs, which had lower CD40 expression, exhibited a decreased ability to induce T-cell proliferation. The presence of MRS1754, a highly selective A2B adenosine receptor antagonist at the time of infection increased MHC class II, CD86 and CD40 expression in L. amazonensis-infected DCs and restored the ability of the infected DCs to induce T-cell proliferation. Similar results were obtained through the inhibition of extracellular ATP hydrolysis using suramin. In conclusion, we propose that A2B receptor activation may be used by L. amazonensis to inhibit DC function and evade the immune response.

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