@article{894c6ebac06741c4adf1e9b996a93924,
title = "Dengue Virus Infects Human Skin Langerhans Cells through Langerin for Dissemination to Dendritic Cells",
abstract = "Dengue virus (DENV) is the most disease-causative flavivirus worldwide. DENV as a mosquito-borne virus infects human hosts through the skin; however, the initial target cells in the skin remain unclear. In this study, we have investigated whether epidermal Langerhans cells (LCs) play a role in DENV acquisition and dissemination. We have used a human epidermal ex vivo infection model as well as isolated LCs to investigate infection by DENV. Notably, both immature and mature LCs were permissive to DENV infection in vitro and ex vivo, and infection was dependent on C-type lectin receptor langerin because blocking antibodies against langerin significantly reduced DENV infection in vitro and ex vivo. DENV-infected LCs efficiently transmitted DENV to target cells such as dendritic cells. Moreover, DENV exposure increased the migration of LCs from epidermal explants. These results strongly suggest that DENV targets epidermal LCs for infection and dissemination in the human host. These findings could provide potential drug targets to combat the early stage of DENV infection.",
keywords = "Dendritic cells, Dengue virus, Langerhans cells, Langerin, Transmission",
author = "Helgers, {Leanne C.} and Keijzer, {Nadia C. H.} and {van Hamme}, {John L.} and Sprokholt, {Joris K.} and Geijtenbeek, {Teunis B. H.}",
note = "Funding Information: K. Luhn (University of Oxford, Oxford, United Kingdom) provided Dengue virus type 2/16681. M. van Hemert (Leiden University Medical Center, Leiden, The Netherlands) provided C6/36 cells. We thank C. Ribeiro for discussions regarding the role of Langerhans cells in Dengue virus infection. We thank E.J. Kooi for providing cytokeratin AE-1/AE-3 antibodies. This work was supported by the European Research Council (TBHG, Advanced grant 670424 ). Funding Information: K. Luhn (University of Oxford, Oxford, United Kingdom) provided Dengue virus type 2/16681. M. van Hemert (Leiden University Medical Center, Leiden, The Netherlands) provided C6/36 cells. We thank C. Ribeiro for discussions regarding the role of Langerhans cells in Dengue virus infection. We thank E.J. Kooi for providing cytokeratin AE-1/AE-3 antibodies. This work was supported by the European Research Council (TBHG, Advanced grant 670424). Conceptualization: TBHG, JKS, LCH; Data Curation: LCH, NK, JLvH; Formal Analysis: LCH; Funding Acquisition: TBHG; Investigation: LCH; Methodology: LCH, JKS; Project Administration: LH; Resources: TBHG; Supervision: TBHG; Validation: LCH; Writing – Original Draft Preparation: LCH; Writing – Review and Editing: LCH, TBHG, JKS, NK Publisher Copyright: {\textcopyright} 2023 The Authors",
year = "2023",
doi = "https://doi.org/10.1016/j.jid.2023.09.287",
language = "English",
journal = "Journal of Investigative Dermatology",
issn = "0022-202X",
publisher = "Nature Publishing Group",
}