Human anogenital monocyte-derived dendritic cells and langerin+cDC2 are major HIV target cells

Jake W. Rhodes, Rachel A. Botting, Kirstie M. Bertram, Erica E. Vine, Hafsa Rana, Heeva Baharlou, Peter Vegh, Thomas R. O’Neil, Anneliese S. Ashhurst, James Fletcher, Grant P. Parnell, J. Dinny Graham, Najla Nasr, Jake J. K. Lim, Laith Barnouti, Peter Haertsch, Martijn P. Gosselink, Angelina Di Re, Faizur Reza, Grahame Ctercteko, Gregory J. Jenkins, Andrew J. Brooks, Ellis Patrick, Scott N. Byrne, Eric Hunter, Muzlifah A. Haniffa, Anthony L. Cunningham and Andrew N. Harman ()
Additional contact information
Jake W. Rhodes: The Westmead Institute for Medical Research
Rachel A. Botting: The Westmead Institute for Medical Research
Kirstie M. Bertram: The Westmead Institute for Medical Research
Erica E. Vine: The Westmead Institute for Medical Research
Hafsa Rana: The Westmead Institute for Medical Research
Heeva Baharlou: The Westmead Institute for Medical Research
Peter Vegh: The University of Newcastle
Thomas R. O’Neil: The Westmead Institute for Medical Research
Anneliese S. Ashhurst: The University of Sydney
James Fletcher: The University of Newcastle
Grant P. Parnell: The Westmead Institute for Medical Research
J. Dinny Graham: The Westmead Institute for Medical Research
Najla Nasr: The Westmead Institute for Medical Research
Jake J. K. Lim: Dr Jake Lim PLC
Laith Barnouti: Australia Plastic Surgery
Peter Haertsch: Burns Unit, Concord Repatriation General Hospital
Martijn P. Gosselink: The Westmead Institute for Medical Research
Angelina Di Re: The Westmead Institute for Medical Research
Faizur Reza: The Westmead Institute for Medical Research
Grahame Ctercteko: The Westmead Institute for Medical Research
Gregory J. Jenkins: Westmead Hospital
Andrew J. Brooks: Westmead Hospital
Ellis Patrick: The Westmead Institute for Medical Research
Scott N. Byrne: The Westmead Institute for Medical Research
Eric Hunter: Emory Vaccine Centre
Muzlifah A. Haniffa: The University of Newcastle
Anthony L. Cunningham: The Westmead Institute for Medical Research
Andrew N. Harman: The Westmead Institute for Medical Research

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: Abstract Tissue mononuclear phagocytes (MNP) are specialised in pathogen detection and antigen presentation. As such they deliver HIV to its primary target cells; CD4 T cells. Most MNP HIV transmission studies have focused on epithelial MNPs. However, as mucosal trauma and inflammation are now known to be strongly associated with HIV transmission, here we examine the role of sub-epithelial MNPs which are present in a diverse array of subsets. We show that HIV can penetrate the epithelial surface to interact with sub-epithelial resident MNPs in anogenital explants and define the full array of subsets that are present in the human anogenital and colorectal tissues that HIV may encounter during sexual transmission. In doing so we identify two subsets that preferentially take up HIV, become infected and transmit the virus to CD4 T cells; CD14+CD1c+ monocyte-derived dendritic cells and langerin-expressing conventional dendritic cells 2 (cDC2).

Date: 2021
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DOI: 10.1038/s41467-021-22375-x

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