Cerny Daniela, Haniffa Muzlifah, Shin Amanda, Bigliardi Paul, Tan Bien Keem, Lee Bernett, Poidinger Michael, Tan Ern Yu, Ginhoux Florent, Fink Katja
Singapore Immunology Network, Agency for Science, Technology and Research, Singapore; School of Biological Sciences, Nanyang Technological University, Singapore.
Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
PLoS Pathog. 2014 Dec 4;10(12):e1004548. doi: 10.1371/journal.ppat.1004548. eCollection 2014 Dec.
Dengue is a growing global concern with 390 million people infected each year. Dengue virus (DENV) is transmitted by mosquitoes, thus host cells in the skin are the first point of contact with the virus. Human skin contains several populations of antigen-presenting cells which could drive the immune response to DENV in vivo: epidermal Langerhans cells (LCs), three populations of dermal dendritic cells (DCs), and macrophages. Using samples of normal human skin we detected productive infection of CD14(+) and CD1c(+) DCs, LCs and dermal macrophages, which was independent of DC-SIGN expression. LCs produced the highest viral titers and were less sensitive to IFN-β. Nanostring gene expression data showed significant up-regulation of IFN-β, STAT-1 and CCL5 upon viral exposure in susceptible DC populations. In mice infected intra-dermally with DENV we detected parallel populations of infected DCs originating from the dermis and migrating to the skin-draining lymph nodes. Therefore dermal DCs may simultaneously facilitate systemic spread of DENV and initiate the adaptive anti-viral immune response.
登革热是一个日益引起全球关注的问题，每年有3.9亿人感染。登革病毒（DENV）通过蚊子传播，因此皮肤中的宿主细胞是与该病毒的首个接触点。人类皮肤含有多种抗原呈递细胞群体，它们可在体内驱动针对DENV的免疫反应：表皮朗格汉斯细胞（LCs）、三种真皮树突状细胞（DCs）群体以及巨噬细胞。使用正常人皮肤样本，我们检测到CD14(+)和CD1c(+) DCs、LCs以及真皮巨噬细胞发生了有效感染，这与DC-SIGN表达无关。LCs产生的病毒滴度最高，且对IFN-β不太敏感。纳米串基因表达数据显示，在易感DC群体中，病毒暴露后IFN-β、STAT-1和CCL5显著上调。在经皮内感染DENV的小鼠中，我们检测到源自真皮并迁移至引流皮肤淋巴结的平行感染DC群体。因此，真皮DCs可能同时促进DENV的全身传播并启动适应性抗病毒免疫反应。
