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Exclusive Expression of MyD88 on Dendritic Cells Is Lopez Kostka Sufficient to Induce Protection against Experimental Leishmaniasis

  • Author Footnotes
    5 These authors contributed equally to this work.
    Susanna Lopez Kostka
    Footnotes
    5 These authors contributed equally to this work.
    Affiliations
    Department of Dermatology and Venereology, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany
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  • Author Footnotes
    5 These authors contributed equally to this work.
    Kordula Kautz-Neu
    Footnotes
    5 These authors contributed equally to this work.
    Affiliations
    Department of Dermatology and Venereology, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany
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  • Author Footnotes
    5 These authors contributed equally to this work.
    Nir Yogev
    Footnotes
    5 These authors contributed equally to this work.
    Affiliations
    Department of Dermatology and Venereology, Faculty of Medicine, University of Cologne, Cologne, Germany
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  • Dominika Lukas
    Affiliations
    Department of Dermatology and Venereology, Faculty of Medicine, University of Cologne, Cologne, Germany
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  • Bernhard Holzmann
    Affiliations
    Department of Surgery, Faculty of Medicine, Technische Universität München, Munich, Germany
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  • Ari Waisman
    Affiliations
    Institute for Molecular Medicine Mainz, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany
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    6 These authors contributed equally to this work.
    Björn E. Clausen
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    6 These authors contributed equally to this work.
    Affiliations
    Institute for Molecular Medicine Mainz, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany
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    6 These authors contributed equally to this work.
    Esther von Stebut
    Correspondence
    Corresponding author
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    6 These authors contributed equally to this work.
    Affiliations
    Department of Dermatology and Venereology, Faculty of Medicine, University of Cologne, Cologne, Germany
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  • Author Footnotes
    5 These authors contributed equally to this work.
    6 These authors contributed equally to this work.
Published:September 24, 2021DOI:https://doi.org/10.1016/j.jid.2021.07.184
      Leishmania parasites, endemic in (sub)tropical regions, cause a neglected tropical disease affecting ∼12 million cases worldwide. The spectrum of pathologies ranges from cutaneous leishmaniasis to progressive fatal visceral disease. Both in humans and mice, healing is associated with successful development of IFN-γ‒producing T helper type (Th)1/Tc1 cells, whereas Th2-, Th17-, and regulatory T-cell‒predominant responses are associated with progression and/or nonhealing lesions (
      • Kautz-Neu K.
      • Noordegraaf M.
      • Dinges S.
      • Bennett C.L.
      • John D.
      • Clausen B.E.
      • et al.
      Langerhans cells are negative regulators of the anti-Leishmania response.
      ;
      • Sacks D.
      • Noben-Trauth N.
      The immunology of susceptibility and resistance to Leishmania major in mice.
      ). After transmission, Leishmania major primarily resides in skin-resident macrophages. Lesion infiltrating IFN-γ+ T cells activate macrophages to eliminate parasites through nitric oxide (
      • Sacks D.
      • Noben-Trauth N.
      The immunology of susceptibility and resistance to Leishmania major in mice.
      ). In contrast to the silent invasion of macrophages, parasite internalization by dendritic cells (DCs) triggers DC activation (
      • Woelbing F.
      • Susanna L.K.
      • Moelle K.
      • Belkaid Y.
      • Sunderkoetter C.
      • Verbeek S.
      • et al.
      Uptake of Leishmania major by dendritic cells is mediated by Fcgamma receptors and facilitates acquisition of protective immunity.
      ), and infected DCs are considered to induce protection by IL-12 (
      • von Stebut E.
      • Belkaid Y.
      • Jakob T.
      • Sacks D.L.
      • Udey M.C.
      Uptake of Leishmania major amastigotes results in activation and interleukin 12 release from murine skin-derived dendritic cells: implications for the initiation of anti-Leishmania immunity.
      ) and by priming T cells against L. major antigens. These early events after parasite inoculation are critical for disease outcome.

      Abbreviations:

      DC (dendritic cell), Th (T helper type), TLR (toll-like receptor)
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