Selective susceptibility of human skin antigen presenting cells to productive dengue virus infection.(PLoS Pathog. 2014 Dec 4;10(12):e1004548)

報告日期: 2015/03/24
報告時間: 17:10/18:00
報告學生: 吳宇軒
講評老師: 彭貴春
附件下載: 下載[1458-1425857152-1.pdf] 

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

Daniela Cerny, Muzlifah Haniffa, Amanda Shin, Paul Bigliardi, Bien Keem Tan, Bernett Lee, Michael Poidinger, Ern Yu Tan, Florent Ginhoux, Katja Fink*

PLoS Pathog. 2014 Dec 4;10(12):e1004548.

Speaker: Yu-Hsuan Wu (吳宇軒)                                     Time: 17:00-17:50, Mar. 24, 2015

Commentator: Guey-Chuen Perng, Ph.D. (彭貴春)           Room: 602

Abstract

  Dengue virus (DENV) is an arthropod-borne pathogen, which infects 390 million people in the world and causes dengue fever (DF). There are 10-50% of DENV patients get the severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), resulting in tens of thousands of deaths annually1. Dengue virus is transmitted by mosquitoes biting skin. Human skin contains epidermal Langerhans Cells (LCs), three subsets of dermal dendritic cells (DDCs) and macrophages. While pathogen infection, LCs and DCs will migrate to draining lymph modes (LNs) and activate down-stream adaptive immune responses2. Previous studies have proposed that LCs and DCs are the major targets of DENV infection. Especially, DCs expressing DC-SIGN have been well-described to contribute to virus infection. However, the detail mechanisms of the interaction of immune cells and DENV is still unclear. In this study, the human skin tissue was used to clarify the mechanism in response to DENV infection in vivo. The authors found that the antigen presenting cells (APCs) were susceptibility to DENV infection, which was independently correlated with DS-SIGN. CD14+ DCs and LCs were infected most efficiently, but LCs produced highest titer of virions and less sensitive to IFN-β. The Nanostring data and chemotaxis assay also indicated that the DENV-susceptible DCs up-regulated innate immune-related genes followed with stimulating DCs migration upon DENV infection. These results were further confirmed in mice model, which demonstrated that DENV infection rapidly stimulated immune response to prompt migration of infected DCs into lymph nodes. In conclusion, DENV selectively infects human skin APCs and stimulates adaptive immune responses for systemic spread of DENV.

References:

1  Morrison, J. et al. Dengue virus co-opts UBR4 to degrade STAT2 and antagonize type I interferon signaling. PLoS pathogens 9, e1003265, doi:10.1371/journal.ppat.1003265 (2013).

2  Bustos-Arriaga, J. et al. Activation of the innate immune response against DENV in normal non-transformed human fibroblasts. PLoS neglected tropical diseases 5, e1420, doi:10.1371/journal.pntd.0001420 (2011).