Identification of HIV transmitting CD11c+ human epidermal dendritic cells

被引:84
作者
Bertram, Kirstie M. [1 ,2 ]
Botting, Rachel A. [1 ,2 ,3 ]
Baharlou, Heeva [1 ,2 ]
Rhodes, Jake W. [1 ,2 ]
Rana, Hafsa [1 ,2 ]
Graham, J. Dinny [1 ,2 ]
Patrick, Ellis [1 ,2 ]
Fletcher, James [3 ]
Plasto, Toby M. [1 ,2 ]
Truong, Naomi R. [1 ,2 ]
Royle, Caroline [1 ,2 ]
Doyle, Chloe M. [1 ,2 ]
Tong, Orion [1 ,2 ]
Nasr, Najla [1 ,2 ]
Barnouti, Laith [4 ]
Kohout, Mark P. [4 ]
Brooks, Andrew J. [5 ]
Wines, Michael P. [6 ]
Haertsch, Peter [7 ]
Lim, Jake [8 ]
Gosselink, Martijn P. [1 ,5 ]
Ctercteko, Grahame [1 ,5 ]
Estes, Jacob D. [9 ]
Churchill, Melissa J. [10 ]
Cameron, Paul U. [11 ]
Hunter, Eric [12 ]
Haniffa, Muzlifah A. [3 ,13 ]
Cunningham, Anthony L. [1 ,2 ]
Harman, Andrew N. [1 ,2 ]
机构
[1] Westmead Inst Med Res, Ctr Virus Res, 176 Hawkesbury Rd, Westmead, NSW 2145, Australia
[2] Univ Sydney, Sydney, NSW 2006, Australia
[3] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England
[4] Australia Plast Surg, 185-211 Broadway, Sydney, NSW 2007, Australia
[5] Westmead Hosp, Westmead, NSW 2145, Australia
[6] Royal North Shore Hosp, Reserve Rd, St Leonards, NSW 2065, Australia
[7] Concord Repatriat Gen Hosp, Burns Unit, Sydney, NSW 2139, Australia
[8] Dr Jake Lim PLC, Shop 12,Cnr Aird & Marsden St, Parramatta, NSW 2150, Australia
[9] Leidos Biomed Res Inc, AIDS & Canc Virus Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA
[10] RMIT Univ, Coll Sci Engn & Hlth, Sch Hlth & Biomed Sci, Melbourne, Vic 3001, Australia
[11] Peter Doherty Inst Infect & Immun, 792 Elizabeth St, Melbourne, Vic 3000, Australia
[12] Emory Vaccine Ctr, 954 Gatewood Rd, Atlanta, GA 30329 USA
[13] Newcastle Hosp NHS Fdn Trust, Royal Victoria Infirm, Dept Dermatol, Newcastle Upon Tyne NE2 4LP, Tyne & Wear, England
基金
英国医学研究理事会; 英国惠康基金; 美国国家卫生研究院;
关键词
LANGERHANS CELLS; RNA-SEQ; INFECTION; EXPRESSION; SKIN; TRANSMISSION; MACROPHAGES; INDUCTION; FORESKIN; DISTINCT;
D O I
10.1038/s41467-019-10697-w
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
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 CD33(low) 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.
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页数:15
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