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; Andrew N. Harman

doi:10.1038/s41467-019-10697-w

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 journal › Article › peer-review

54 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 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.

Original language	English (US)
Article number	2759
Journal	Nature communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-10697-w
State	Published - Dec 1 2019
Externally published	Yes

ASJC Scopus subject areas

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

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10.1038/s41467-019-10697-w

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Bertram, K. M., Botting, R. A., Baharlou, H., Rhodes, J. W., Rana, H., Graham, J. D., Patrick, E., Fletcher, J., Plasto, T. M., Truong, N. R., Royle, C., Doyle, C. M., Tong, O., Nasr, N., Barnouti, L., Kohout, M. P., Brooks, A. J., Wines, M. P., Haertsch, P., ... Harman, A. N. (2019). Identification of HIV transmitting CD11c⁺ human epidermal dendritic cells. Nature communications, 10(1), [2759]. https://doi.org/10.1038/s41467-019-10697-w

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 2019, 'Identification of HIV transmitting CD11c⁺ human epidermal dendritic cells', Nature communications, vol. 10, no. 1, 2759. https://doi.org/10.1038/s41467-019-10697-w

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title = "Identification of HIV transmitting CD11c+ human epidermal dendritic cells",

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.",

author = "Bertram, {Kirstie M.} and Botting, {Rachel A.} and Heeva Baharlou and Rhodes, {Jake W.} and Hafsa Rana and Graham, {J. Dinny} and Ellis Patrick and James Fletcher and Plasto, {Toby M.} and Truong, {Naomi R.} and Caroline Royle and Doyle, {Chloe M.} and Orion Tong and Najla Nasr and Laith Barnouti and Kohout, {Mark P.} and Brooks, {Andrew J.} and Wines, {Michael P.} and Peter Haertsch and Jake Lim and Gosselink, {Martijn P.} and Grahame Ctercteko and Estes, {Jacob D.} and Churchill, {Melissa J.} and Cameron, {Paul U.} and Eric Hunter and Haniffa, {Muzlifah A.} and Cunningham, {Anthony L.} and Harman, {Andrew N.}",

note = "Funding Information: Flow cytometry and cell imaging were performed in the Flow Cytometry Core Facility and Cell Imaging Core Facility that are supported by Westmead Institute, Westmead Research Hub, Cancer Institute New South Wales and National Health and Medical Research Council. Immunofluorescence microscopy imaging was also performed in the ithree Institute, University of Technology Sydney. This work was funded by the National Health and Medical Research Council (Australia) the Wellcome Trust (WT107931/Z/15/ Z), the Lister Institute and the NIHR Newcastle Biomedical Research Centre. This project has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. Publisher Copyright: {\textcopyright} 2019, The Author(s).",

year = "2019",

month = dec,

day = "1",

doi = "10.1038/s41467-019-10697-w",

language = "English (US)",

volume = "10",

journal = "Nature Communications",

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T1 - Identification of HIV transmitting CD11c+ human epidermal dendritic cells

AU - Bertram, Kirstie M.

AU - Botting, Rachel A.

AU - Baharlou, Heeva

AU - Rhodes, Jake W.

AU - Rana, Hafsa

AU - Graham, J. Dinny

AU - Patrick, Ellis

AU - Fletcher, James

AU - Plasto, Toby M.

AU - Truong, Naomi R.

AU - Royle, Caroline

AU - Doyle, Chloe M.

AU - Tong, Orion

AU - Nasr, Najla

AU - Barnouti, Laith

AU - Kohout, Mark P.

AU - Brooks, Andrew J.

AU - Wines, Michael P.

AU - Haertsch, Peter

AU - Lim, Jake

AU - Gosselink, Martijn P.

AU - Ctercteko, Grahame

AU - Estes, Jacob D.

AU - Churchill, Melissa J.

AU - Cameron, Paul U.

AU - Hunter, Eric

AU - Haniffa, Muzlifah A.

AU - Cunningham, Anthony L.

AU - Harman, Andrew N.

N1 - Funding Information: Flow cytometry and cell imaging were performed in the Flow Cytometry Core Facility and Cell Imaging Core Facility that are supported by Westmead Institute, Westmead Research Hub, Cancer Institute New South Wales and National Health and Medical Research Council. Immunofluorescence microscopy imaging was also performed in the ithree Institute, University of Technology Sydney. This work was funded by the National Health and Medical Research Council (Australia) the Wellcome Trust (WT107931/Z/15/ Z), the Lister Institute and the NIHR Newcastle Biomedical Research Centre. This project has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. Publisher Copyright: © 2019, The Author(s).

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

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VL - 10

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 2759

ER -

Identification of HIV transmitting CD11c⁺ human epidermal dendritic cells

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