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.

Details

Title
Identification of HIV transmitting CD11c+ human epidermal dendritic cells
Author
Bertram, Kirstie M 1 ; Botting, Rachel A 2 ; Baharlou, Heeva 1 ; Rhodes, Jake W 1   VIAFID ORCID Logo  ; Rana, Hafsa 1 ; Graham, J Dinny 1 ; Ellis, Patrick 1   VIAFID ORCID Logo  ; Fletcher, James 3 ; Plasto, Toby M 1 ; Truong, Naomi R 1 ; Royle, Caroline 1 ; Doyle, Chloe M 1   VIAFID ORCID Logo  ; Tong, Orion 1 ; Nasr, Najla 1 ; Barnouti, Laith 4 ; Kohout, Mark P 4 ; Brooks, Andrew J 5 ; Wines, Michael P 6 ; Haertsch, Peter 7 ; Lim, Jake 8 ; Gosselink, Martijn P 9   VIAFID ORCID Logo  ; Ctercteko, Grahame 9 ; Estes, Jacob D 10 ; Churchill, Melissa J 11 ; Cameron, Paul U 12   VIAFID ORCID Logo  ; Hunter, Eric 13   VIAFID ORCID Logo  ; Haniffa, Muzlifah A 14   VIAFID ORCID Logo  ; Cunningham, Anthony L 1 ; Harman, Andrew N 1   VIAFID ORCID Logo 

1  Centre for Virus Research, The Westmead Institute for Medical Research, Westmead, New South Wales, Australia; The University of Sydney, Sydney, New South Wales, Australia 
2  Centre for Virus Research, The Westmead Institute for Medical Research, Westmead, New South Wales, Australia; The University of Sydney, Sydney, New South Wales, Australia; Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK 
3  Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK 
4  Australia Plastic Surgery, Sydney, New South Wales, Australia 
5  Westmead Hospital, Westmead, New South Wales, Australia 
6  Royal North Shore Hospital, St Leonards, New South Wales, Australia 
7  Burns Unit, Concord Repatriation General Hospital, Sydney, New South Wales, Australia 
8  Dr Jake Lim PLC, Parramatta, New South Wales, Australia 
9  Centre for Virus Research, The Westmead Institute for Medical Research, Westmead, New South Wales, Australia; Westmead Hospital, Westmead, New South Wales, Australia 
10  AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc, Frederick, MD, USA 
11  School of Health and Biomedical Sciences, College of Science, Engineering and Health, RMIT University, Melbourne, Victoria, Australia 
12  The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia 
13  Emory Vaccine Center, Atlanta, GA, USA 
14  Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK; Department of Dermatology, Royal Victoria Infirmary, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK 
Pages
1-15
Publication year
2019
Publication date
Jun 2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-019-10697-w
ProQuest document ID
2244645629
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.