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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.02697

Cathelicidin contributes to the restriction of Leishmania in human host macrophages

  • 1Head of the Immunolgy Division, Paul Ehrlich Institut, Germany
  • 2Institute of Microbiology and Biotechnology, Fakultät für Naturwissenschaften, Universität Ulm, Germany
  • 3Department of Immunology, Paul Ehrlich Institute, Germany
  • 4Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Sweden
  • 5Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Sweden
  • 6Armauer Hansen Research Institute (AHRI), Ethiopia
  • 7Paul Ehrlich Institut, Germany
  • 8Regensburg Center for Interventional Immunology (RCI), Germany
  • 9Research Center Borstel (LG), Germany

In cutaneous Leishmaniasis the parasitic control in human host macrophages is still poorly understood. We found an increased expression of the human cathelicidin CAMP in skin lesions of Ethiopian patients with cutaneous leishmaniasis. Vitamin D driven, Cathelicidin-type antimicrobial peptides (CAMP) play an important role in the elimination of invading microorganisms. Recombinant cathelicidin was able to induce cell-death characteristics in Leishmania in a dose dependent manner. Using human primary macrophages, we demonstrated pro-inflammatory macrophages (hMDM1) to express a higher level of human cathelicidin, both on gene and protein level, compared to anti-inflammatory macrophages (hMDM2). Activating the CAMP pathway using Vitamin D in hMDM1 resulted in a cathelicidin-mediated-Leishmania restriction. Finally, a reduction of cathelicidin in hMDM1, using a RNA interference (RNAi) approach, increased Leishmania parasite survival. In all, these data show the human cathelicidin to contribute to the innate immune response against Leishmaniasis in a human primary cell model.

Keywords: Leishmania, human macrophages, Vitamin D, cathelicidin (LL-37), human primary immune cells, Antimicrobial actibity

Received: 03 May 2019; Accepted: 01 Nov 2019.

Copyright: © 2019 van Zandbergen, Crauwels, Bank, walbers, Wenzel, Agerberth, Negatue, Alemayehu, König, Ritter and Reiling. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Ger van Zandbergen, Paul Ehrlich Institut, Head of the Immunolgy Division, Langen, Germany, ger.zandbergen@pei.de