Dendritic cells treated with crude Plasmodium berghei extracts acquire immune-modulatory properties and suppress the development of autoimmune neuroinflammation

Authors

  • Rodolfo Thomé,

    1. Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil
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  • Luidy K. Issayama,

    1. Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil
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  • Thiago Alves da Costa,

    1. Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil
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  • Rosária D. Gangi,

    1. Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil
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  • Isadora T. Ferreira,

    1. Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil
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  • Catarina Rapôso,

    1. Department of Histology and Embryology, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil
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  • Stefanie C. P. Lopes,

    1. Department of Genetics, Evolution and Bioagents, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil
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  • Maria Alice da Cruz Höfling,

    1. Department of Histology and Embryology, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil
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  • Fábio T. M. Costa,

    1. Department of Genetics, Evolution and Bioagents, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil
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  • Liana Verinaud

    Corresponding author
    1. Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil
    • Correspondence: Liana Verinaud, Institute of Biology, State University of Campinas, Rua Monteiro Lobato 255, Cidade Universitária, SP 13083-862, Brazil.

      Email: verinaud@unicamp.br

      Senior author: Liana Verinaud

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Summary

Dendritic cells (DCs) are professional antigen-presenting cells specifically targeted during Plasmodium infection. Upon infection, DCs show impaired antigen presentation and T-cell activation abilities. In this study, we aimed to evaluate whether cellular extracts obtained from Plasmodium berghei-infected erythrocytes (PbX) modulate DCs phenotypically and functionally and the potential therapeutic usage of PbX-modulated DCs in the control of experimental autoimmune encephalomyelitis (EAE, the mouse model for human multiple sclerosis). We found that PbX-treated DCs have impaired maturation and stimulated the generation of regulatory T cells when cultured with naive T lymphocytes in vitro. When adoptively transferred to C57BL/6 mice the EAE severity was reduced. Disease amelioration correlated with a diminished infiltration of cytokine-producing T cells in the central nervous system as well as the suppression of encephalitogenic T cells. Our study shows that extracts obtained from P. berghei-infected erythrocytes modulate DCs towards an immunosuppressive phenotype. In addition, the adoptive transfer of PbX-modulated DCs was able to ameliorate EAE development through the suppression of specific cellular immune responses towards neuro-antigens. To our knowledge, this is the first study to present evidence that DCs treated with P. berghei extracts are able to control autoimmune neuroinflammation.

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