Altered innate immune response of plasmacytoid dendritic cells in multiple sclerosis

Authors

  • A. Bayas,

    Corresponding author
    1. Department of Neurology, University of Würzburg, Würzburg,
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    • Present address: Department of Neurology, Klinikum Augsburg, Stenglinstr. 2, 86156 Augsburg, Germany.

    • These authors contributed equally to the work.

  • M. Stasiolek,

    1. Department of Neurology, Medical University of Lodz, Lodz, Poland
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    • Present address: Department of Neurology, Ruhr-University Bochum, 44791 Bochum, Germany.

    • These authors contributed equally to the work.

  • N. Kruse,

    1. Institute for MS-Research, Medical Faculty of the University and Gemeinnuetzige Hertie-Stiftung, Waldweg, Goettingen, Germany, and
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    • These authors contributed equally to the work.

  • K. V. Toyka,

    1. Department of Neurology, University of Würzburg, Würzburg,
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  • K. Selmaj,

    1. Department of Neurology, Medical University of Lodz, Lodz, Poland
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    • These senior authors contributed equally to the work.

  • R. Gold

    1. Institute for MS-Research, Medical Faculty of the University and Gemeinnuetzige Hertie-Stiftung, Waldweg, Goettingen, Germany, and
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    • Present address: Department of Neurology, Ruhr-University Bochum, 44791 Bochum, Germany.

    • These senior authors contributed equally to the work.

    • Senior author's e-mail: ralf.gold@ruhr-uni-bochum.de


Summary

Plasmacytoid dendritic cells (pDCs) are of crucial importance in immune regulation and response to microbial factors. In multiple sclerosis (MS), pDCs from peripheral blood showed an immature phenotype, but its role in susceptibility to MS is not determined. Because infectious diseases are established triggers of exacerbations in MS, in this study we have characterized the expression of Toll-like receptors (TLR) and the maturation and functional properties of peripheral blood pDCs from clinically stable, untreated MS patients in response to signals of innate immunity. After stimulation of TLR-9, interferon (IFN)-α production by pDCs was significantly lower in MS (n = 12) compared to healthy controls (n = 9). In an allogenic two-step co-culture assay we found an impaired effect of TLR-9 stimulation on IFN-γ expression of autologous naive T cells in MS patients (n = 4). In peripheral blood mononuclear cells, TLR-9 stimulation with type A CpG ODN resulted in a higher expression of TLR-1, -2, -4, -5 and -8 in MS patients (n = 7) compared with healthy controls (n = 11). These findings suggest an altered innate immune response to microbial stimuli in MS patients and may help understanding of why common infectious agents trigger MS attacks.

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