Innate Immune Response to Influenza Virus at Single-Cell Resolution in Human Epithelial Cells Revealed Paracrine Induction of Interferon Lambda 1.

Autor:	Ramos I; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA irene.ramos-lopez@mssm.edu ana.sesma@mssm.edu., Smith G; Department of Neurology, Center for Advanced Research on Diagnostic Assays, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Ruf-Zamojski F; Department of Neurology, Center for Advanced Research on Diagnostic Assays, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Martínez-Romero C; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Fribourg M; Department of Neurology, Center for Advanced Research on Diagnostic Assays, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Carbajal EA; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; The Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Hartmann BM; Department of Neurology, Center for Advanced Research on Diagnostic Assays, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Nair VD; Department of Neurology, Center for Advanced Research on Diagnostic Assays, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Marjanovic N; Department of Neurology, Center for Advanced Research on Diagnostic Assays, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Monteagudo PL; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA., DeJesus VA; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Mutetwa T; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; The Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Zamojski M; Department of Neurology, Center for Advanced Research on Diagnostic Assays, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Tan GS; Infectious Diseases, J. Craig Venter Institute, La Jolla, California, USA.; Department of Medicine, University of California San Diego, La Jolla, California, USA., Jayaprakash C; Department of Physics, The Ohio State University, Columbus, Ohio, USA., Zaslavsky E; Department of Neurology, Center for Advanced Research on Diagnostic Assays, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Albrecht RA; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; The Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Sealfon SC; Department of Neurology, Center for Advanced Research on Diagnostic Assays, Icahn School of Medicine at Mount Sinai, New York, New York, USA., García-Sastre A; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Fernandez-Sesma A; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA irene.ramos-lopez@mssm.edu ana.sesma@mssm.edu.; The Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Jazyk:	angličtina
Zdroj:	Journal of virology [J Virol] 2019 Sep 30; Vol. 93 (20). Date of Electronic Publication: 2019 Sep 30 (Print Publication: 2019).
DOI:	10.1128/JVI.00559-19
Abstrakt:	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. IMPORTANCE Influenza A virus (IAV) is a respiratory pathogen of high importance to public health. Annual epidemics of seasonal IAV infections in humans are a significant public health and economic burden. IAV also causes sporadic pandemics, which can have devastating effects. The main target cells for IAV replication are epithelial cells in the respiratory epithelium. The cellular innate immune responses induced in these cells upon infection are critical for defense against the virus, and therefore, it is important to understand the complex interactions between the virus and the host cells. In this study, we investigated the innate immune response to IAV in the respiratory epithelium at the single-cell level, providing a better understanding on how a population of epithelial cells functions as a complex system to orchestrate the response to virus infection and how the virus counteracts this system. (Copyright © 2019 Ramos et al.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu