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Lookup NU author(s): Professor Muzlifah Haniffa
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Copyright: © 2024 Warner van Dijk et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. AXL+ Siglec-6+ dendritic cells (ASDC) are novel myeloid DCs which can be subdivided into CD11c+ and CD123+ expressing subsets. We showed for the first time that these two ASDC subsets are present in inflamed human anogenital tissues where HIV transmission occurs. Their presence in inflamed tissues was supported by single cell RNA analysis of public databases of such tissues including psoriasis diseased skin and colorectal cancer. Almost all previous studies have examined ASDCs as a combined population. Our data revealed that the two ASDC subsets differ markedly in their functions when compared with each other and to pDCs. Relative to their cell functions, both subsets of blood ASDCs but not pDCs expressed co-stimulatory and maturation markers which were more prevalent on CD11c+ ASDCs, thus inducing more T cell proliferation and activation than their CD123+ counterparts. There was also a significant polarisation of naïve T cells by both ASDC subsets toward Th2, Th9, Th22, Th17 and Treg but less toward a Th1 phenotype. Furthermore, we investigated the expression of chemokine receptors that facilitate ASDCs and pDCs migration from blood to inflamed tissues, their HIV binding receptors, and their interactions with HIV and CD4 T cells. For HIV infection, within 2 hours of HIV exposure, CD11c+ ASDCs showed a trend in more viral transfer to T cells than CD123+ ASDCs and pDCs for first phase transfer. However, for second phase transfer, CD123+ ASDCs showed a trend in transferring more HIV than CD11c+ ASDCs and there was no viral transfer from pDCs. As anogenital inflammation is a prerequisite for HIV transmission, strategies to inhibit ASDC recruitment into inflamed tissues and their ability to transmit HIV to CD4 T cells should be considered.
Author(s): Warner van Dijk FA, Tong O, O'Neil TR, Bertram KM, Hu K, Baharlou H, Vine EE, Jenns K, Gosselink MP, Toh JW, Papadopoulos T, Barnouti L, Jenkins GJ, Sandercoe G, Haniffa M, Sandgren KJ, Harman AN, Cunningham AL, Nasr N
Publication type: Article
Publication status: Published
Journal: PLoS Pathogens
Year: 2024
Volume: 20
Online publication date: 26/06/2024
Acceptance date: 18/06/2024
Date deposited: 26/07/2024
ISSN (print): 1553-7366
ISSN (electronic): 1553-7374
Publisher: Public Library of Science
URL: https://doi.org/10.1371/journal.ppat.1012351
DOI: 10.1371/journal.ppat.1012351
Data Access Statement: All relevant data are within the manuscript and its Supporting information files.
PubMed id: 38924030
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