Identification of HIV-Transmitting Sub-Epithelial Mononuclear Phagocytes in Human Anogenital and Colorectal Tissues

Jake W Rhodes, et al.

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Received Date: 15th May 20

Jake W Rhodes, Rachel A Botting, Kirstie M Bertram, Hafsa Rana, Heeva Baharlou, Erica E Longmuir-Vine, Peter Vegh, James Fletcher, Thomas R O’Neil, Grant P Parnell, J Dinny Graham, Najla Nasr, Jake J K Lim, Laith Barnouti, Peter Haertsch, Martijn P Gosselink, Angelina Di Re, Grahame Ctercteko, Gregory J Jenkins, Andrew J Brooks, Ellis Patrick, Scott N Byrne, Muzlifah A Haniffa, Anthony L Cunningham, Andrew N Harman

Tissue mononuclear phagocytes (MNP) are specialised in pathogen detection and antigen presentation. They are the first cells of the immune system to encounter HIV and play a key role in transmission as they deliver the virus to CD4 T cells, which are the primary HIV target cell in which the virus undergoes replication. Most studies have investigated the role that epithelial MNPs play in HIV transmission but, as mucosal trauma and inflammation are strongly associated with HIV transmission, it is also important to examine the role that sub-epithelial MNPs play. Sub-epithelial MNPs are present in a diverse array of subsets which differ in their function and the pathogens they detect. Understanding how specific subsets interact with HIV and deliver the virus to CD4 T cells is therefore of key importance to vaccine and microbicide development. In this study we have shown that, after topical application, HIV can penetrate to interact with sub-epithelial resident myeloid cells in anogenital explants and defined the full array of MNP subsets that are present in all the human anogenital and colorectal sub-epithelial tissues that HIV may encounter during sexual transmission. In doing so we have identified two subsets that preferentially take up HIV, become infected and transmit the virus to CD4 T cells; CD14+CD1c+CD11c+ monocyte-derived dendritic cells and langerin-expressing dendritic cells 2 (DC2). Tissue mononuclear phagocytes (MNP) are specialised in pathogen detection and antigen presentation. They are the first cells of the immune system to encounter HIV and play a key role in transmission as they deliver the virus to CD4 T cells, which are the primary HIV target cell in which the virus undergoes replication. Most studies have investigated the role that epithelial MNPs play in HIV transmission but, as mucosal trauma and inflammation are strongly associated with HIV transmission, it is also important to examine the role that sub-epithelial MNPs play. Sub-epithelial MNPs are present in a diverse array of subsets which differ in their function and the pathogens they detect. Understanding how specific subsets interact with HIV and deliver the virus to CD4 T cells is therefore of key importance to vaccine and microbicide development. In this study we have shown that, after topical application, HIV can penetrate to interact with sub-epithelial resident myeloid cells in anogenital explants and defined the full array of MNP subsets that are present in all the human anogenital and colorectal sub-epithelial tissues that HIV may encounter during sexual transmission. In doing so we have identified two subsets that preferentially take up HIV, become infected and transmit the virus to CD4 T cells; CD14+CD1c+CD11c+ monocyte-derived dendritic cells and langerin-expressing dendritic cells 2 (DC2).

Read in full at bioRxiv.

This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

Nature Communications

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