Cargando…

Single-cell glycomics analysis by CyTOF-Lec reveals glycan features defining cells differentially susceptible to HIV

High-parameter single-cell phenotyping has enabled in-depth classification and interrogation of immune cells, but to date has not allowed for glycan characterization. Here, we develop CyTOF-Lec as an approach to simultaneously characterize many protein and glycan features of human immune cells at th...

Descripción completa

Detalles Bibliográficos
Autores principales: Ma, Tongcui, McGregor, Matthew, Giron, Leila, Xie, Guorui, George, Ashley F, Abdel-Mohsen, Mohamed, Roan, Nadia R
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9255966/
https://www.ncbi.nlm.nih.gov/pubmed/35787792
http://dx.doi.org/10.7554/eLife.78870
_version_ 1784741021090840576
author Ma, Tongcui
McGregor, Matthew
Giron, Leila
Xie, Guorui
George, Ashley F
Abdel-Mohsen, Mohamed
Roan, Nadia R
author_facet Ma, Tongcui
McGregor, Matthew
Giron, Leila
Xie, Guorui
George, Ashley F
Abdel-Mohsen, Mohamed
Roan, Nadia R
author_sort Ma, Tongcui
collection PubMed
description High-parameter single-cell phenotyping has enabled in-depth classification and interrogation of immune cells, but to date has not allowed for glycan characterization. Here, we develop CyTOF-Lec as an approach to simultaneously characterize many protein and glycan features of human immune cells at the single-cell level. We implemented CyTOF-Lec to compare glycan features between different immune subsets from blood and multiple tissue compartments, and to characterize HIV-infected cell cultures. Using bioinformatics approaches to distinguish preferential infection of cellular subsets from viral-induced remodeling, we demonstrate that HIV upregulates the levels of cell-surface fucose and sialic acid in a cell-intrinsic manner, and that memory CD4+ T cells co-expressing high levels of fucose and sialic acid are highly susceptible to HIV infection. Sialic acid levels were found to distinguish memory CD4+ T cell subsets expressing different amounts of viral entry receptors, pro-survival factors, homing receptors, and activation markers, and to play a direct role in memory CD4+ T cells’ susceptibility to HIV infection. The ability of sialic acid to distinguish memory CD4+ T cells with different susceptibilities to HIV infection was experimentally validated through sorting experiments. Together, these results suggest that HIV remodels not only cellular proteins but also glycans, and that glycan expression can differentiate memory CD4+ T cells with vastly different susceptibility to HIV infection.
format Online
Article
Text
id pubmed-9255966
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher eLife Sciences Publications, Ltd
record_format MEDLINE/PubMed
spelling pubmed-92559662022-07-06 Single-cell glycomics analysis by CyTOF-Lec reveals glycan features defining cells differentially susceptible to HIV Ma, Tongcui McGregor, Matthew Giron, Leila Xie, Guorui George, Ashley F Abdel-Mohsen, Mohamed Roan, Nadia R eLife Immunology and Inflammation High-parameter single-cell phenotyping has enabled in-depth classification and interrogation of immune cells, but to date has not allowed for glycan characterization. Here, we develop CyTOF-Lec as an approach to simultaneously characterize many protein and glycan features of human immune cells at the single-cell level. We implemented CyTOF-Lec to compare glycan features between different immune subsets from blood and multiple tissue compartments, and to characterize HIV-infected cell cultures. Using bioinformatics approaches to distinguish preferential infection of cellular subsets from viral-induced remodeling, we demonstrate that HIV upregulates the levels of cell-surface fucose and sialic acid in a cell-intrinsic manner, and that memory CD4+ T cells co-expressing high levels of fucose and sialic acid are highly susceptible to HIV infection. Sialic acid levels were found to distinguish memory CD4+ T cell subsets expressing different amounts of viral entry receptors, pro-survival factors, homing receptors, and activation markers, and to play a direct role in memory CD4+ T cells’ susceptibility to HIV infection. The ability of sialic acid to distinguish memory CD4+ T cells with different susceptibilities to HIV infection was experimentally validated through sorting experiments. Together, these results suggest that HIV remodels not only cellular proteins but also glycans, and that glycan expression can differentiate memory CD4+ T cells with vastly different susceptibility to HIV infection. eLife Sciences Publications, Ltd 2022-07-05 /pmc/articles/PMC9255966/ /pubmed/35787792 http://dx.doi.org/10.7554/eLife.78870 Text en © 2022, Ma et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Immunology and Inflammation
Ma, Tongcui
McGregor, Matthew
Giron, Leila
Xie, Guorui
George, Ashley F
Abdel-Mohsen, Mohamed
Roan, Nadia R
Single-cell glycomics analysis by CyTOF-Lec reveals glycan features defining cells differentially susceptible to HIV
title Single-cell glycomics analysis by CyTOF-Lec reveals glycan features defining cells differentially susceptible to HIV
title_full Single-cell glycomics analysis by CyTOF-Lec reveals glycan features defining cells differentially susceptible to HIV
title_fullStr Single-cell glycomics analysis by CyTOF-Lec reveals glycan features defining cells differentially susceptible to HIV
title_full_unstemmed Single-cell glycomics analysis by CyTOF-Lec reveals glycan features defining cells differentially susceptible to HIV
title_short Single-cell glycomics analysis by CyTOF-Lec reveals glycan features defining cells differentially susceptible to HIV
title_sort single-cell glycomics analysis by cytof-lec reveals glycan features defining cells differentially susceptible to hiv
topic Immunology and Inflammation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9255966/
https://www.ncbi.nlm.nih.gov/pubmed/35787792
http://dx.doi.org/10.7554/eLife.78870
work_keys_str_mv AT matongcui singlecellglycomicsanalysisbycytoflecrevealsglycanfeaturesdefiningcellsdifferentiallysusceptibletohiv
AT mcgregormatthew singlecellglycomicsanalysisbycytoflecrevealsglycanfeaturesdefiningcellsdifferentiallysusceptibletohiv
AT gironleila singlecellglycomicsanalysisbycytoflecrevealsglycanfeaturesdefiningcellsdifferentiallysusceptibletohiv
AT xieguorui singlecellglycomicsanalysisbycytoflecrevealsglycanfeaturesdefiningcellsdifferentiallysusceptibletohiv
AT georgeashleyf singlecellglycomicsanalysisbycytoflecrevealsglycanfeaturesdefiningcellsdifferentiallysusceptibletohiv
AT abdelmohsenmohamed singlecellglycomicsanalysisbycytoflecrevealsglycanfeaturesdefiningcellsdifferentiallysusceptibletohiv
AT roannadiar singlecellglycomicsanalysisbycytoflecrevealsglycanfeaturesdefiningcellsdifferentiallysusceptibletohiv