NDLI: Langerhans Cell-Dendritic Cell Cross-Talk via Langerin and Hyaluronic Acid Mediates Antigen Transfer and Cross-Presentation of HIV-1.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Van Den Berg, Linda M. Sprokholt, Joris K. de Jong, Marein A. W. P. Zijlstra-Willems, Esther M. Moris, Arnaud Cardinaud, Sylvain Geijtenbeek, Teunis B. H. Van Der Aar, Angelic M. G.
Description	Author Affiliation: van den Berg LM ( Department of Experimental Immunology, Academic Medical Center, 1105 AZ Amsterdam, the Netherlands); Cardinaud S ( Center for Immunology and Microbial Infections-Paris, University Pierre and Marie Curie Paris 06, University Sorbonne, F-75013 Paris, France); van der Aar AM ( Department of Experimental Immunology, Academic Medical Center, 1105 AZ Amsterdam, the Netherlands); Sprokholt JK ( Department of Experimental Immunology, Academic Medical Center, 1105 AZ Amsterdam, the Netherlands); de Jong MA ( Department of Experimental Immunology, Academic Medical Center, 1105 AZ Amsterdam, the Netherlands); Zijlstra-Willems EM ( Department of Experimental Immunology, Academic Medical Center, 1105 AZ Amsterdam, the Netherlands); Moris A ( Center for Immunology and Microbial Infections-Paris, University Pierre and Marie Curie Paris 06, University Sorbonne, F-75013 Paris, France); Geijtenbeek TB ( Department of Experimental Immunology, Academic Medical Center, 1105 AZ Amsterdam, the Netherlands)
Abstract	Human epidermal and mucosal Langerhans cells (LCs) express the C-type lectin receptor langerin that functions as a pattern recognition receptor. LCs are among the first immune cells to interact with HIV-1 during sexual transmission. In this study, we demonstrate that langerin not only functions as a pattern recognition receptor but also as an adhesion receptor mediating clustering between LCs and dendritic cells (DCs). Langerin recognized hyaluronic acid on DCs and removal of these carbohydrate structures partially abrogated LC-DC clustering. Because LCs did not cross-present HIV-1-derived Ags to CD8(+) T cells in a cross-presentation model, we investigated whether LCs were able to transfer Ags to DCs. LC-DC clustering led to maturation of DCs and facilitated Ag transfer of HIV-1 to DCs, which subsequently induced activation of CD8(+) cells. The rapid transfer of Ags to DCs, in contrast to productive infection of LCs, suggests that this might be an important mechanism for induction of anti-HIV-1 CD8(+) T cells. Induction of the enzyme hyaluronidase-2 by DC maturation allowed degradation of hyaluronic acid and abrogated LC-DC interactions. Thus, we have identified an important function of langerin in mediating LC-DC clustering, which allows Ag transfer to induce CTL responses to HIV-1. Furthermore, we showed this interaction is mediated by hyaluronidase-2 upregulation after DC maturation. These data underscore the importance of LCs and DCs in orchestrating adaptive immunity to HIV-1. Novel strategies might be developed to harness this mechanism for vaccination.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	4
Volume Number	195
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2015-08-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Antigen Presentation Immunology Antigens, Cd Metabolism Cell Communication Dendritic Cells Hyaluronic Acid Langerhans Cells Lectins, C-type Mannose-binding Lectins Cd8-positive T-lymphocytes Drug Effects Cross-priming Hiv Antigens Hiv Infections Hiv-1 Pharmacology Ligands Protein Binding Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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