Characterising plasmacytoid and myeloid AXL+ SIGLEC-6+ dendritic cell functions and their interactions with HIV.

Autor: Warner van Dijk FA; The Westmead Institute for Medical Research, Centre for Virus Research, Westmead, Australia.; The University of Sydney, School of Medical Sciences, Faculty of Medicine and Health, Sydney, Australia., Tong O; The Westmead Institute for Medical Research, Centre for Virus Research, Westmead, Australia., O'Neil TR; The Westmead Institute for Medical Research, Centre for Virus Research, Westmead, Australia.; The University of Sydney, School of Medical Sciences, Faculty of Medicine and Health, Sydney, Australia., Bertram KM; The Westmead Institute for Medical Research, Centre for Virus Research, Westmead, Australia., Hu K; The Westmead Institute for Medical Research, Centre for Virus Research, Westmead, Australia.; The University of Sydney, School of Medical Sciences, Faculty of Medicine and Health, Sydney, Australia., Baharlou H; The Westmead Institute for Medical Research, Centre for Virus Research, Westmead, Australia.; The University of Sydney, School of Medical Sciences, Faculty of Medicine and Health, Sydney, Australia., Vine EE; The Westmead Institute for Medical Research, Centre for Virus Research, Westmead, Australia.; The University of Sydney, School of Medical Sciences, Faculty of Medicine and Health, Sydney, Australia., Jenns K; The Westmead Institute for Medical Research, Centre for Virus Research, Westmead, Australia.; The University of Sydney, School of Medical Sciences, Faculty of Medicine and Health, Sydney, Australia., Gosselink MP; Department of Colorectal Surgery, Westmead Hospital, Westmead, Australia., Toh JW; The Westmead Institute for Medical Research, Centre for Virus Research, Westmead, Australia.; The University of Sydney, School of Medical Sciences, Faculty of Medicine and Health, Sydney, Australia.; Department of Colorectal Surgery, Westmead Hospital, Westmead, Australia., Papadopoulos T; Department of Plastic, Reconstructive, and Aesthetic Surgery, Westmead Private Hospital, Westmead, Australia., Barnouti L; Department of Plastic, Reconstructive, and Aesthetic Surgery, Westmead Private Hospital, Westmead, Australia., Jenkins GJ; Department of Obstetrics and Gynaecology, Westmead Hospital, Westmead, Australia., Sandercoe G; Department of Plastic Surgery, Norwest Private Hospital, Bella Vista, Australia., Haniffa M; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, United Knigdom.; Biosciences Institute, Newcastle University, Newcastle, United Knigdom.; Department of Dermatology and NIHR Newcastle Biomedical Research Centre, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Knigdom., Sandgren KJ; The Westmead Institute for Medical Research, Centre for Virus Research, Westmead, Australia.; The University of Sydney, School of Medical Sciences, Faculty of Medicine and Health, Sydney, Australia., Harman AN; The Westmead Institute for Medical Research, Centre for Virus Research, Westmead, Australia.; The University of Sydney, School of Medical Sciences, Faculty of Medicine and Health, Sydney, Australia., Cunningham AL; The Westmead Institute for Medical Research, Centre for Virus Research, Westmead, Australia.; The University of Sydney, School of Medical Sciences, Faculty of Medicine and Health, Sydney, Australia., Nasr N; The Westmead Institute for Medical Research, Centre for Virus Research, Westmead, Australia.; The University of Sydney, School of Medical Sciences, Faculty of Medicine and Health, Sydney, Australia.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2024 Jun 26; Vol. 20 (6), pp. e1012351. Date of Electronic Publication: 2024 Jun 26 (Print Publication: 2024).
DOI: 10.1371/journal.ppat.1012351
Abstrakt: 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.
Competing Interests: The authors have declared that no competing interests exist.
(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.)
Databáze: MEDLINE
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