Identification of HIV transmitting CD11c+ human epidermal dendritic cells.,Nature Communications

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Identification of HIV transmitting CD11c+ human epidermal dendritic cells.
Nature Communications ( IF 14.7 ) Pub Date : 2019-06-21 , DOI: 10.1038/s41467-019-10697-w
Kirstie M Bertram _{1,

2} , Rachel A Botting _{1,

2,

3} , Heeva Baharlou _{1,

2} , Jake W Rhodes _{1,

2} , Hafsa Rana _{1,

2} , J Dinny Graham _{1,

2} , Ellis Patrick _{1,

2} , James Fletcher ₃ , Toby M Plasto _{1,

2} , Naomi R Truong _{1,

2} , Caroline Royle _{1,

2} , Chloe M Doyle _{1,

2} , Orion Tong _{1,

2} , Najla Nasr _{1,

2} , Laith Barnouti ₄ , Mark P Kohout ₄ , Andrew J Brooks ₅ , Michael P Wines ₆ , Peter Haertsch ₇ , Jake Lim ₈ , Martijn P Gosselink _{1,

5} , Grahame Ctercteko _{1,

5} , Jacob D Estes ₉ , Melissa J Churchill ₁₀ , Paul U Cameron ₁₁ , Eric Hunter ₁₂ , Muzlifah A Haniffa _{3,

13} , Anthony L Cunningham _{1,

2} , Andrew N Harman _{1,

2}

Affiliation

Centre for Virus Research, The Westmead Institute for Medical Research, 176 Hawkesbury Road, Westmead, New South Wales, 2145, Australia.
The University of Sydney, Sydney, 2006, New South Wales, Australia.
Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
Australia Plastic Surgery, 185-211, Broadway, Sydney, New South Wales, 2007, Australia.
Westmead Hospital, Westmead, New South Wales, 2145, Australia.
Royal North Shore Hospital, Reserve Rd, St Leonards, New South Wales, 2065, Australia.
Burns Unit, Concord Repatriation General Hospital, Sydney, 2139, New South Wales, Australia.
Dr Jake Lim PLC, Shop 12, Cnr of Aird & Marsden Street, Parramatta, New South Wales, 2150, Australia.
AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc, Frederick, MD, 21702, USA.
School of Health and Biomedical Sciences, College of Science, Engineering and Health, RMIT University, Melbourne, Victoria, 3001, Australia.
The Peter Doherty Institute for Infection and Immunity, 792 Elizabeth Street, Melbourne, Victoria, 3000, Australia.
Emory Vaccine Center, 954 Gatewood Road, Atlanta, GA, 30329, USA.
Department of Dermatology, Royal Victoria Infirmary, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, NE2 4LP, UK.

Langerhans cells (LC) are thought to be the only mononuclear phagocyte population in the epidermis where they detect pathogens. Here, we show that CD11c+ dendritic cells (DCs) are also present. These cells are transcriptionally similar to dermal cDC2 but are more efficient antigen-presenting cells. Compared to LCs, epidermal CD11c+ DCs are enriched in anogenital tissues where they preferentially interact with HIV, express the higher levels of HIV entry receptor CCR5, support the higher levels of HIV uptake and replication and are more efficient at transmitting the virus to CD4 T cells. Importantly, these findings are observed using both a lab-adapted and transmitted/founder strain of HIV. We also describe a CD33low cell population, which is transcriptionally similar to LCs but does not appear to function as antigen-presenting cells or acts as HIV target cells. Our findings reveal that epidermal DCs in anogenital tissues potentially play a key role in sexual transmission of HIV.

中文翻译：

鉴定HIV传播的CD11c +人表皮树突状细胞。

朗格汉斯细胞（LC）被认为是表皮中唯一可检测病原体的单核吞噬细胞。在这里，我们显示CD11c +树突状细胞（DC）也存在。这些细胞在转录上与真皮cDC2相似，但它们是更有效的抗原呈递细胞。与LC相比，表皮CD11c + DC富集在生殖器组织中，它们优先与HIV相互作用，表达更高水平的HIV进入受体CCR5，支持更高水平的HIV吸收和复制，并且更有效地将病毒传播给CD4 T细胞。重要的是，使用实验室适应的和传播/基础的HIV毒株都可以观察到这些发现。我们还描述了CD33low细胞群，它在转录上与LC相似，但似乎不充当抗原呈递细胞或充当HIV靶细胞。我们的发现表明，肛门生殖器组织中的表皮DC可能在HIV的性传播中起关键作用。

更新日期：2019-06-21

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