%A Zimara,Nicole
%A Chanyalew,Menberework
%A Aseffa,Abraham
%A van Zandbergen,Ger
%A Lepenies,Bernd
%A Schmid,Maximilian
%A Weiss,Richard
%A Rascle,Anne
%A Wege,Anja Kathrin
%A Jantsch,Jonathan
%A Schatz,Valentin
%A Brown,Gordon D.
%A Ritter,Uwe
%D 2018
%J Frontiers in Immunology
%C
%F
%G English
%K Curdlan,β-Glucan,dectin-1,cutaneous leishmaniasis,Adaptive Immunity,Dendritic Cells,Th1 and Th2 cells
%Q
%R 10.3389/fimmu.2018.00263
%W
%L
%M
%P
%7
%8 2018-February-26
%9 Original Research
%+ Dr Uwe Ritter,Regensburg Center for Interventional Immunology (RCI), Institute of Immunology, University Medical Center Regensburg, University of Regensburg,Germany,uwe.ritter@ukr.de
%#
%! Running title: Immunmodulation in experimental leishmaniasis
%*
%<
%T Dectin-1 Positive Dendritic Cells Expand after Infection with Leishmania major Parasites and Represent Promising Targets for Vaccine Development
%U https://www.frontiersin.org/articles/10.3389/fimmu.2018.00263
%V 9
%0 JOURNAL ARTICLE
%@ 1664-3224
%X 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 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 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 induces 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: wild-type 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 L. major 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.