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, Péter Végh, Thomas R. O’Neil, Anneliese S. Ashhurst, James Fletcher, Grant P. Parnell, J. Dinny Graham, Najla Nasr, Jake Lim, Laith Barnouti, Peter Haertsch, M. Gosselink, Angelina Di Re, Faizur Reza, Grahame Ctercteko, Gregory J. Jenkins, Andrew J. Brooks, Ellis Patrick, Scott N. Byrne, Eric Hunter, Muzlifah Haniffa, Anthony L. Cunningham, Andrew N. Harman
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).