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

Author:

Ramos Irene1ORCID,Smith Gregory2,Ruf-Zamojski Frederique2,Martínez-Romero Carles13,Fribourg Miguel2,Carbajal Edwin A.14,Hartmann Boris M.2,Nair Venugopalan D.2,Marjanovic Nada2,Monteagudo Paula L.1ORCID,DeJesus Veronica A.1,Mutetwa Tinaye14,Zamojski Michel2,Tan Gene S.56,Jayaprakash Ciriyam7,Zaslavsky Elena2,Albrecht Randy A.14ORCID,Sealfon Stuart C.2,García-Sastre Adolfo183,Fernandez-Sesma Ana14

Affiliation:

1. Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA

2. Department of Neurology, Center for Advanced Research on Diagnostic Assays, Icahn School of Medicine at Mount Sinai, New York, New York, USA

3. Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA

4. The Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA

5. Infectious Diseases, J. Craig Venter Institute, La Jolla, California, USA

6. Department of Medicine, University of California San Diego, La Jolla, California, USA

7. Department of Physics, The Ohio State University, Columbus, Ohio, USA

8. Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA

Abstract

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.

Funder

HHS | National Institutes of Health

HHS | NIH | National Institute of Allergy and Infectious Diseases

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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