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Nat Commun. 2019 Jun 21;10(1):2759. doi: 10.1038/s41467-019-10697-w.

Identification of HIV transmitting CD11c+ human epidermal dendritic cells.

Author information

1
Centre for Virus Research, The Westmead Institute for Medical Research, 176 Hawkesbury Road, Westmead, New South Wales, 2145, Australia.
2
The University of Sydney, Sydney, 2006, New South Wales, Australia.
3
Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
4
Australia Plastic Surgery, 185-211, Broadway, Sydney, New South Wales, 2007, Australia.
5
Westmead Hospital, Westmead, New South Wales, 2145, Australia.
6
Royal North Shore Hospital, Reserve Rd, St Leonards, New South Wales, 2065, Australia.
7
Burns Unit, Concord Repatriation General Hospital, Sydney, 2139, New South Wales, Australia.
8
Dr Jake Lim PLC, Shop 12, Cnr of Aird & Marsden Street, Parramatta, New South Wales, 2150, Australia.
9
AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc, Frederick, MD, 21702, USA.
10
School of Health and Biomedical Sciences, College of Science, Engineering and Health, RMIT University, Melbourne, Victoria, 3001, Australia.
11
The Peter Doherty Institute for Infection and Immunity, 792 Elizabeth Street, Melbourne, Victoria, 3000, Australia.
12
Emory Vaccine Center, 954 Gatewood Road, Atlanta, GA, 30329, USA.
13
Department of Dermatology, Royal Victoria Infirmary, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, NE2 4LP, UK.
14
Centre for Virus Research, The Westmead Institute for Medical Research, 176 Hawkesbury Road, Westmead, New South Wales, 2145, Australia. andrew.harman@sydney.edu.au.
15
The University of Sydney, Sydney, 2006, New South Wales, Australia. andrew.harman@sydney.edu.au.

Abstract

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.

PMID:
31227717
PMCID:
PMC6588576
DOI:
10.1038/s41467-019-10697-w
[Indexed for MEDLINE]
Free PMC Article

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