Original Research ARTICLE
Dectin-1 positive dendritic cells expand after infection with Leishmania major parasites and represent promising targets for vaccine development
- 1Immunology, University of Regensburg, Germany
- 2Armauer Hansen Research Institute, Ethiopia
- 3Paul Ehrlich Institut, Germany
- 4University of Veterinary Medicine Hannover, Germany
- 5Department of Molecular Biology, Division of Allergy and Immunology, University of Salzburg, Salzburg, Austria, Austria
- 6Department of Gynecology and Obstetrics, University Medical Center Regensburg, Regensburg, Germany, Germany
- 7MRC Centre for Medical Mycology, University of Aberdeen, Aberdeen, United Kingdom, United Kingdom
Resistant mouse strains mount a protective T cell mediated immune response upon infection with Leishmania (L.) parasites. Healing correlates with a T helper (Th) cell type 1 response, characterized by a pronounced IFN-γ production while susceptibility is associated with an IL-4 dependent Th2-type response. It has been shown that dermal dendritic cells (DC) are crucial for inducing protective Th1-mediated immunity. Additionally, there is growing evidence that C-type lectin receptor (CLR)-mediated signaling is involved in directing adaptive immunity against pathogens. However, little is known about the function of the CLR Dectin-1 in modulating Th1- or Th2-type immune responses by DC subsets in leishmaniasis.
We characterized the expression of Dectin-1 on CD11c+ DCs in peripheral blood, at the site of infection, and skin-draining lymph nodes (SDLN) of L. major infected C57BL/6 and BALB/c mice and in peripheral blood of patients suffering from cutaneous leishmaniasis (CL). Both mouse strains responded with an expansion of Dectin-1+ DCs within the analyzed tissues. In accordance with the experimental model, Dectin-1+ DCs expanded as well in the peripheral blood of CL patients.
To study the role of Dectin-1+ DCs in adaptive immunity against L. major, we analyzed the T cell stimulating potential of bone marrow-derived dendritic cells (BMDCs) in the presence of the Dectin-1 agonist Curdlan. These experiments revealed that Curdlan increases the maturation of BMDCs and the expansion of Leishmania-specific CD4+ T cells.
Based on these findings, we evaluated the impact of Curdlan/Dectin-1 interactions in experimental leishmaniasis and were able to demonstrate that the presence of Curdlan at the site of infection modulates the course of disease in BALB/c mice: Wildtype BALB/c mice treated intradermally with Curdlan developed a protective immune response against L. major whereas Dectin-1-/- BALB/c mice still developed the fatal course of disease after Curdlan treatment. Furthermore, the vaccination of BALB/c mice with a combination of soluble Leishmania antigens and Curdlan was able to provide a partial protection from severe leishmaniasis.
These findings indicate that the ligation of Dectin-1 on DCs acts as an important checkpoint in adaptive immunity against L. major and should therefore be considered in future whole- organism vaccination strategies.
Keywords: Curdlan, β-Glucan, dectin-1, cutaneous leishmaniasis, Adaptive Immunity, Dendritic Cells, Th1 and Th2 cells
Received: 05 Oct 2017;
Accepted: 30 Jan 2018.
Edited by:Abhay Satoskar, The Ohio State University, United States
Reviewed by:Peter E. Kima, University of Florida, United States
Reto Guler, University of Cape Town, South Africa
Copyright: © 2018 Zimara, Chanyalew, Aseffa, van Zandbergen, Lepenies, Schmid, Weiss, Rascle, Wege, Brown and Ritter. 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 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: Prof. Uwe Ritter, University of Regensburg, Immunology, Franz-Josef-Strauss-Allee 11, Regensburg, 93053, Bavaria, Germany, firstname.lastname@example.org