Centre for Virus Research, The Westmead Institute for Medical Research, Westmead, NSW, Australia.
Westmead Clinical School, Faculty of Medicine and Health Sydney, The University of Sydney, Westmead, NSW, Australia.
Nat Commun. 2021 Apr 12;12(1):2147. doi: 10.1038/s41467-021-22375-x.
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; CD14CD1c monocyte-derived dendritic cells and langerin-expressing conventional dendritic cells 2 (cDC2).
组织单核吞噬细胞（MNP）专门用于病原体检测和抗原呈递。因此，它们将 HIV 递送到其主要靶细胞；CD4 T 细胞。大多数 MNP HIV 传播研究都集中在上皮 MNP 上。然而，由于现在已知粘膜创伤和炎症与 HIV 传播密切相关，我们在这里研究了存在于多种亚群中的粘膜下 MNP 的作用。我们表明，HIV 可以穿透上皮表面，与肛门生殖器外植体中的粘膜下常驻 MNP 相互作用，并确定 HIV 在性传播过程中可能遇到的人肛门生殖器和结直肠组织中存在的所有亚群。通过这样做，我们确定了两个优先摄取 HIV、感染并将病毒传播给 CD4 T 细胞的亚群；CD14CD1c 单核细胞衍生的树突状细胞和朗格汉斯表达的常规树突状细胞 2（cDC2）。
