Dengue virus infects human skin Langerhans cells via langerin for dissemination to dendritic cells

Leanne C Helgers; Nadia C H Keijzer; John L van Hamme; Joris Sprokholt; Teunis B H Geijtenbeek

doi:10.1016/j.jid.2023.09.287

Dengue virus infects human skin Langerhans cells via langerin for dissemination to dendritic cells

J Invest Dermatol. 2023 Nov 16:S0022-202X(23)03056-7. doi: 10.1016/j.jid.2023.09.287. Online ahead of print.

Authors

Leanne C Helgers¹, Nadia C H Keijzer¹, John L van Hamme¹, Joris Sprokholt¹, Teunis B H Geijtenbeek²

Affiliations

¹ Amsterdam UMC, University of Amsterdam, Department of Experimental Immunology, Amsterdam institute for Infection & Immunity, Meibergdreef 9, Amsterdam, The Netherlands.
² Amsterdam UMC, University of Amsterdam, Department of Experimental Immunology, Amsterdam institute for Infection & Immunity, Meibergdreef 9, Amsterdam, The Netherlands. Electronic address: t.b.geijtenbeek@amsterdamumc.nl.

PMID: 37979773
DOI: 10.1016/j.jid.2023.09.287

Abstract

Dengue virus (DENV) is the most disease causative flavivirus worldwide. DENV as a mosquito-borne virus infects human hosts via the skin, however the initial target cells in the skin remain unclear. Here, 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 as 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 (DCs). Moreover, DENV exposure increased 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 early stage of DENV infection.

Keywords: Langerhans cells; dendritic cells; dengue virus; langerin; transmission.