Identification of HIV Transmitting CD11c+ Human Epidermal Dendritic Cells

Langerhans cells (LC) represent one of the first lines of contact between the immune system and sexually transmitted pathogens, and in the human epidermis LCs have been thought to represent the only mononuclear phagocyte (MNP) population. Here we show an additional epidermal MNP subset that can be distinguished from LCs phenotypically as CD11chi, CD1c+ MR+ (epidermal CD11c+ DCs). These cells are transcriptionally similar to dermal cDC2 but express higher levels of costimulatory markers and are more efficient at T cell stimulation. Importantly, compared to LC, epidermal CD11c+ DCs are i) enriched in the epithelium of anogenital tissues where they preferentially interact with HIV, ii) express the higher levels of the HIV entry receptor CCR5, iii) support the higher levels of HIV uptake and replication and iv) are more efficient at transferring virus to CD4 T cells. Importantly these findings were observed using both a lab-adapted and transmitted/founder strain of HIV. We also describe a cell population that can be discerned from LCs by their lower surface expression of CD45, HLA-DR and CD33 (epidermal CD33low cells). These are transcriptionally similar to LCs but do not appear to function as APCs as do not secrete cytokines, express negligible amounts of costimulatory molecules and are very weak inducers of T cell proliferation. They also do not act as HIV target cells. Our findings reveal a new subset of epidermal DCs in skin and anogenital tissues with a potential key role in sexual transmission of HIV. Overall design: Sorted cell populations from four donors were captured directly into lysis buffer and polyA RNA transcripts were reverse transcribed, amplified and sequenced using the Smart-seq 2 protocol described by Picelli et al (Nature Methods. 2013;10(11):1096-8). Each sample was sequenced across 4 HiSeq lanes and the data for each lane is represented as an independent sample (GSM).

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Bertram KM, Botting RA, Baharlou H, Rhodes JW, Rana H, Graham JD, Patrick E, Fletcher J, Plasto TM, Truong NR, Royle C, Doyle CM, Tong O, Nasr N, Barnouti L, Kohout MP, Brooks AJ, Wines MP, Haertsch P, Lim J, Gosselink MP, Ctercteko G, Estes JD, Churchill MJ, Cameron PU, Hunter E, Haniffa MA, Cunningham AL, Harman AN