Innate Immune Response to Influenza Virus at Single-Cell Resolution in Human Epithelial Cells Revealed Paracrine Induction of Interferon Lambda 1.
Epithelial Cells
/ metabolism
Gene Expression Profiling
Gene Expression Regulation, Viral
Host-Pathogen Interactions
/ genetics
Humans
Immunity, Innate
/ genetics
Influenza A virus
/ genetics
Influenza, Human
/ genetics
Interferons
/ biosynthesis
Interleukins
/ biosynthesis
Respiratory Mucosa
/ immunology
Single-Cell Analysis
Viral Nonstructural Proteins
/ genetics
epithelial cells
influenza
innate immunity
interferons
single cell
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
15 10 2019
15 10 2019
Historique:
received:
03
04
2019
accepted:
07
07
2019
pubmed:
4
8
2019
medline:
9
6
2020
entrez:
4
8
2019
Statut:
epublish
Résumé
Early interactions of influenza A virus (IAV) with respiratory epithelium might determine the outcome of infection. The study of global cellular innate immune responses often masks multiple aspects of the mechanisms by which populations of cells work as organized and heterogeneous systems to defeat virus infection, and how the virus counteracts these systems. In this study, we experimentally dissected the dynamics of IAV and human epithelial respiratory cell interaction during early infection at the single-cell level. We found that the number of viruses infecting a cell (multiplicity of infection [MOI]) influences the magnitude of virus antagonism of the host innate antiviral response. Infections performed at high MOIs resulted in increased viral gene expression per cell and stronger antagonist effect than infections at low MOIs. In addition, single-cell patterns of expression of interferons (IFN) and IFN-stimulated genes (ISGs) provided important insights into the contributions of the infected and bystander cells to the innate immune responses during infection. Specifically, the expression of multiple ISGs was lower in infected than in bystander cells. In contrast with other IFNs, IFN lambda 1 (IFNL1) showed a widespread pattern of expression, suggesting a different cell-to-cell propagation mechanism more reliant on paracrine signaling. Finally, we measured the dynamics of the antiviral response in primary human epithelial cells, which highlighted the importance of early innate immune responses at inhibiting virus spread.
Identifiants
pubmed: 31375585
pii: JVI.00559-19
doi: 10.1128/JVI.00559-19
pmc: PMC6798124
pii:
doi:
Substances chimiques
interferon-lambda, human
0
Interleukins
0
Viral Nonstructural Proteins
0
Interferons
9008-11-1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : HHSN272201400008C
Pays : United States
Organisme : NIGMS NIH HHS
ID : R25 GM064118
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI117873
Pays : United States
Informations de copyright
Copyright © 2019 Ramos et al.
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