Department of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; Amsterdam institute for Infection & Immunity, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Department of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; Amsterdam institute for Infection & Immunity, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
J Invest Dermatol. 2024 May;144(5):1099-1111.e3. doi: 10.1016/j.jid.2023.09.287. Epub 2023 Nov 17.
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.
登革热病毒（DENV）是全球最具致病性的黄病毒。DENV 是一种通过蚊虫传播的病毒，通过皮肤感染人类宿主；然而，皮肤中的初始靶细胞仍不清楚。在这项研究中，我们研究了表皮朗格汉斯细胞（LC）是否在 DENV 的获取和传播中发挥作用。我们使用了人表皮体外感染模型以及分离的朗格汉斯细胞来研究 DENV 的感染。值得注意的是，未成熟和成熟的 LC 均允许 DENV 在体外和体内感染，并且感染依赖于 C 型凝集素受体 langerin，因为针对 langerin 的阻断抗体可显著减少体外和体内的 DENV 感染。感染 DENV 的 LC 可有效将 DENV 传播给树突状细胞等靶细胞。此外，DENV 暴露可增加 LC 从表皮外植体中的迁移。这些结果强烈表明 DENV 以表皮 LC 为靶标，在人体宿主中进行感染和传播。这些发现可为对抗 DENV 感染的早期阶段提供潜在的药物靶点。
