Selective Susceptibility of Human Skin Antigen Presenting Cells to Productive Dengue Virus Infection

PLoS Pathogens

Katja Fink¹  Michael Poidinger²  Bernett Lee³  Amanda Shin⁴  Bien Keem Tan⁵  Muzlifah Haniffa⁶  Ern Yu Tan⁷  Daniela Cerny⁷  Paul Bigliardi⁷  Florent Ginhoux⁷ 

[1] Department of General Surgery, Tan Tock Seng Hospital, Singapore;Department of Plastic Surgery, Singapore General Hospital, Singapore;Division of Rheumatology, University Medicine Cluster, National University Health System, Singapore;Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom;Institute of Molecular Biology, Agency for Science, Technology and Research, Singapore;School of Biological Sciences, Nanyang Technological University, Singapore;Singapore Immunology Network, Agency for Science, Technology and Research, Singapore

关键词: Skin infections;    Dengue virus;    T cells;    Skin;    Antigen-presenting cells;    Flow cytometry;    Macrophages;    Dermis;   

DOI  :  10.1371/journal.ppat.1004548

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY