Identification of HIV transmitting CD11c+ human epidermal dendritic cells

Kirstie M. Bertram, Rachel A. Botting, Heeva Baharlou, Jake W. Rhodes, Hafsa Rana, J. Dinny Graham, Ellis Patrick, James Fletcher, Toby M. Plasto, Naomi R. Truong, Caroline Royle, Chloe M. Doyle, Orion Tong, Najla Nasr, Laith Barnouti, Mark P. Kohout, Andrew J. Brooks, Michael P. Wines, Peter Haertsch, Jake Lim, Martijn P. Gosselink, Grahame Ctercteko, Jacob D. Estes, Melissa J. Churchill, Paul U. Cameron, Eric Hunter, Muzlifah A. Haniffa, Anthony L. Cunningham and Andrew N. Harman ()
Additional contact information
Kirstie M. Bertram: The Westmead Institute for Medical Research
Rachel A. Botting: The Westmead Institute for Medical Research
Heeva Baharlou: The Westmead Institute for Medical Research
Jake W. Rhodes: The Westmead Institute for Medical Research
Hafsa Rana: The Westmead Institute for Medical Research
J. Dinny Graham: The Westmead Institute for Medical Research
Ellis Patrick: The Westmead Institute for Medical Research
James Fletcher: Newcastle University
Toby M. Plasto: The Westmead Institute for Medical Research
Naomi R. Truong: The Westmead Institute for Medical Research
Caroline Royle: The Westmead Institute for Medical Research
Chloe M. Doyle: The Westmead Institute for Medical Research
Orion Tong: The Westmead Institute for Medical Research
Najla Nasr: The Westmead Institute for Medical Research
Laith Barnouti: Australia Plastic Surgery
Mark P. Kohout: Australia Plastic Surgery
Andrew J. Brooks: Westmead Hospital
Michael P. Wines: Royal North Shore Hospital
Peter Haertsch: Concord Repatriation General Hospital
Jake Lim: Dr Jake Lim PLC
Martijn P. Gosselink: The Westmead Institute for Medical Research
Grahame Ctercteko: The Westmead Institute for Medical Research
Jacob D. Estes: Leidos Biomedical Research Inc
Melissa J. Churchill: RMIT University
Paul U. Cameron: The Peter Doherty Institute for Infection and Immunity
Eric Hunter: Emory Vaccine Center
Muzlifah A. Haniffa: Newcastle University
Anthony L. Cunningham: The Westmead Institute for Medical Research
Andrew N. Harman: The Westmead Institute for Medical Research

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-10697-w

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