Single-Cell Mass Cytometry Analysis of Human Tonsil T Cell Remodeling by Varicella Zoster Virus

Although pathogens must infect differentiated host cells that exhibit substantial diversity, documenting the consequences of infection against this heterogeneity is challenging. Single-cell mass cytometry permits deep profiling based on combinatorial expression of surface and intracellular proteins....

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Main Authors: Nandini Sen, Gourab Mukherjee, Adrish Sen, Sean C. Bendall, Phillip Sung, Garry P. Nolan, Ann M. Arvin
Format: Article
Language:English
Published: Elsevier 2014-07-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124714004938
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author Nandini Sen
Gourab Mukherjee
Adrish Sen
Sean C. Bendall
Phillip Sung
Garry P. Nolan
Ann M. Arvin
author_facet Nandini Sen
Gourab Mukherjee
Adrish Sen
Sean C. Bendall
Phillip Sung
Garry P. Nolan
Ann M. Arvin
author_sort Nandini Sen
collection DOAJ
description Although pathogens must infect differentiated host cells that exhibit substantial diversity, documenting the consequences of infection against this heterogeneity is challenging. Single-cell mass cytometry permits deep profiling based on combinatorial expression of surface and intracellular proteins. We used this method to investigate varicella-zoster virus (VZV) infection of tonsil T cells, which mediate viral transport to skin. Our results indicate that VZV induces a continuum of changes regardless of basal phenotypic and functional T cell characteristics. Contrary to the premise that VZV selectively infects T cells with skin trafficking profiles, VZV infection altered T cell surface proteins to enhance or induce these properties. Zap70 and Akt signaling pathways that trigger such surface changes were activated in VZV-infected naive and memory cells by a T cell receptor (TCR)-independent process. Single-cell mass cytometry is likely to be broadly relevant for demonstrating how intracellular pathogens modulate differentiated cells to support pathogenesis in the natural host.
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spelling doaj.art-b1f5f45ef0eb4859adbccdc38da69a072022-12-21T18:56:49ZengElsevierCell Reports2211-12472014-07-018263364510.1016/j.celrep.2014.06.024Single-Cell Mass Cytometry Analysis of Human Tonsil T Cell Remodeling by Varicella Zoster VirusNandini Sen0Gourab Mukherjee1Adrish Sen2Sean C. Bendall3Phillip Sung4Garry P. Nolan5Ann M. Arvin6Department of Pediatrics, Stanford University, Stanford, CA 94025, USADepartment of Statistics, Stanford University, Stanford, CA 94025, USADepartment of Medicine, Stanford University, Stanford, CA 94025, USADepartment of Microbiology and Immunology, Stanford University, Stanford, CA 94025, USADepartment of Pediatrics, Stanford University, Stanford, CA 94025, USADepartment of Microbiology and Immunology, Stanford University, Stanford, CA 94025, USADepartment of Pediatrics, Stanford University, Stanford, CA 94025, USAAlthough pathogens must infect differentiated host cells that exhibit substantial diversity, documenting the consequences of infection against this heterogeneity is challenging. Single-cell mass cytometry permits deep profiling based on combinatorial expression of surface and intracellular proteins. We used this method to investigate varicella-zoster virus (VZV) infection of tonsil T cells, which mediate viral transport to skin. Our results indicate that VZV induces a continuum of changes regardless of basal phenotypic and functional T cell characteristics. Contrary to the premise that VZV selectively infects T cells with skin trafficking profiles, VZV infection altered T cell surface proteins to enhance or induce these properties. Zap70 and Akt signaling pathways that trigger such surface changes were activated in VZV-infected naive and memory cells by a T cell receptor (TCR)-independent process. Single-cell mass cytometry is likely to be broadly relevant for demonstrating how intracellular pathogens modulate differentiated cells to support pathogenesis in the natural host.http://www.sciencedirect.com/science/article/pii/S2211124714004938
spellingShingle Nandini Sen
Gourab Mukherjee
Adrish Sen
Sean C. Bendall
Phillip Sung
Garry P. Nolan
Ann M. Arvin
Single-Cell Mass Cytometry Analysis of Human Tonsil T Cell Remodeling by Varicella Zoster Virus
Cell Reports
title Single-Cell Mass Cytometry Analysis of Human Tonsil T Cell Remodeling by Varicella Zoster Virus
title_full Single-Cell Mass Cytometry Analysis of Human Tonsil T Cell Remodeling by Varicella Zoster Virus
title_fullStr Single-Cell Mass Cytometry Analysis of Human Tonsil T Cell Remodeling by Varicella Zoster Virus
title_full_unstemmed Single-Cell Mass Cytometry Analysis of Human Tonsil T Cell Remodeling by Varicella Zoster Virus
title_short Single-Cell Mass Cytometry Analysis of Human Tonsil T Cell Remodeling by Varicella Zoster Virus
title_sort single cell mass cytometry analysis of human tonsil t cell remodeling by varicella zoster virus
url http://www.sciencedirect.com/science/article/pii/S2211124714004938
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