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 LimMartijn P. Gosselink, Grahame Ctercteko, Jacob D. Estes, Melissa J. Churchill, Paul U. Cameron, Eric Hunter, Muzlifah A. Haniffa, Anthony L. Cunningham, Andrew N. Harman

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

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.

Original languageEnglish (US)
Article number2759
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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