Human anogenital monocyte-derived dendritic cells and langerin+cDC2 are major HIV target cells.
Jake W RhodesRachel Anne BottingKirstie M BertramErica E VineHafsa RanaHeeva BaharlouPeter VeghThomas R O'NeilAnneliese S AshhurstJames FletcherGrant P ParnellJ Dinny GrahamNajla NasrJake J K LimLaith BarnoutiPeter HaertschMartijn Pieter GosselinkAngelina Marina Di ReFaizur RezaGrahame CterctekoGregory J JenkinsAndrew J BrooksEllis PatrickScott N ByrneEric HunterMuzlifah A HaniffaAnthony L CunninghamAndrew N HarmanPublished in: Nature communications (2021)
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).
Keyphrases
- dendritic cells
- antiretroviral therapy
- hiv positive
- hiv infected
- hiv testing
- human immunodeficiency virus
- hepatitis c virus
- hiv aids
- men who have sex with men
- endothelial cells
- immune response
- peripheral blood
- induced apoptosis
- south africa
- regulatory t cells
- high resolution
- mental health
- cell cycle arrest
- signaling pathway
- gene expression
- single cell
- induced pluripotent stem cells
- real time pcr
- emergency medicine