Centre for Virus Research, The Westmead Institute for Medical Research, 176 Hawkesbury Road, Westmead, NSW 2145, Australia; The University of Sydney, School of Medical Sciences, Faculty of Medicine and Health Sydney, Sydney, NSW, Australia.
Centre for Virus Research, The Westmead Institute for Medical Research, 176 Hawkesbury Road, Westmead, NSW 2145, Australia; The University of Sydney, School of Medical Sciences, Faculty of Medicine and Health Sydney, Sydney, NSW, Australia.
Cell Rep. 2022 Sep 20;40(12):111385. doi: 10.1016/j.celrep.2022.111385.
The initial immune response to HIV determines transmission. However, due to technical limitations we still do not have a comparative map of early mucosal transmission events. By combining RNAscope, cyclic immunofluorescence, and image analysis tools, we quantify HIV transmission signatures in intact human colorectal explants within 2 h of topical exposure. We map HIV enrichment to mucosal dendritic cells (DCs) and submucosal macrophages, but not CD4 T cells, the primary targets of downstream infection. HIV DCs accumulate near and within lymphoid aggregates, which act as early sanctuaries of high viral titers while facilitating HIV passage to the submucosa. Finally, HIV entry induces recruitment and clustering of target cells, facilitating DC- and macrophage-mediated HIV transfer and enhanced infection of CD4 T cells. These data demonstrate a rapid response to HIV structured to maximize the likelihood of mucosal infection and provide a framework for in situ studies of host-pathogen interactions and immune-mediated pathologies.
HIV 的初始免疫反应决定了传播。然而，由于技术限制，我们仍然没有早期黏膜传播事件的比较图谱。通过结合 RNAscope、循环免疫荧光和图像分析工具，我们在人体直肠外植体接受局部暴露后 2 小时内定量分析了 HIV 传输特征。我们将 HIV 丰度定位到黏膜树突状细胞 (DC) 和黏膜下巨噬细胞，但没有定位到 CD4 T 细胞，CD4 T 细胞是下游感染的主要靶标。HIV DC 聚集在淋巴聚集物附近和内部，淋巴聚集物充当高病毒载量的早期庇护所，同时促进 HIV 向黏膜下转移。最后，HIV 进入诱导靶细胞的募集和聚集，促进 DC 和巨噬细胞介导的 HIV 转移，并增强 CD4 T 细胞的感染。这些数据表明了 HIV 快速反应的结构，旨在最大限度地提高黏膜感染的可能性，并为宿主-病原体相互作用和免疫介导的病理学的原位研究提供了框架。
