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Lookup NU author(s): Professor Muzlifah Haniffa
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
© 2022 The Author(s). 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.
Author(s): Baharlou H, Canete N, Vine EE, Hu K, Yuan D, Sandgren KJ, Bertram KM, Nasr N, Rhodes JW, Gosselink MP, Di Re A, Reza F, Ctercteko G, Pathma-Nathan N, Collins G, Toh J, Patrick E, Haniffa MA, Estes JD, Byrne SN, Cunningham AL, Harman AN
Publication type: Article
Publication status: Published
Journal: Cell Reports
Year: 2022
Volume: 40
Issue: 12
Print publication date: 20/09/2022
Online publication date: 20/09/2022
Acceptance date: 29/08/2022
Date deposited: 04/10/2022
ISSN (electronic): 2211-1247
Publisher: Elsevier BV
URL: https://doi.org/10.1016/j.celrep.2022.111385
DOI: 10.1016/j.celrep.2022.111385
PubMed id: 36130503
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