Long-term survival of influenza virus infected club cells drives immunopathology

Nicholas S Heaton; Ryan A Langlois; David Sachs; Jean K Lim; Peter Palese; Benjamin R tenOever

doi:10.1084/jem.20140488

Long-term survival of influenza virus infected club cells drives immunopathology

J Exp Med. 2014 Aug 25;211(9):1707-14. doi: 10.1084/jem.20140488. Epub 2014 Aug 18.

Authors

Nicholas S Heaton¹, Ryan A Langlois², David Sachs¹, Jean K Lim¹, Peter Palese³, Benjamin R tenOever⁴

Affiliations

¹ Department of Microbiology, Global Health and Emerging Pathogens Institute, and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
² Department of Microbiology, Global Health and Emerging Pathogens Institute, and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029 Department of Microbiology, Global Health and Emerging Pathogens Institute, and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
³ Department of Microbiology, Global Health and Emerging Pathogens Institute, and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029 [email protected] [email protected].
⁴ Department of Microbiology, Global Health and Emerging Pathogens Institute, and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029 Department of Microbiology, Global Health and Emerging Pathogens Institute, and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029 [email protected] [email protected].

Abstract

Respiratory infection of influenza A virus (IAV) is frequently characterized by extensive immunopathology and proinflammatory signaling that can persist after virus clearance. In this report, we identify cells that become infected, but survive, acute influenza virus infection. We demonstrate that these cells, known as club cells, elicit a robust transcriptional response to virus infection, show increased interferon stimulation, and induce high levels of proinflammatory cytokines after successful viral clearance. Specific depletion of these surviving cells leads to a reduction in lung tissue damage associated with IAV infection. We propose a model in which infected, surviving club cells establish a proinflammatory environment aimed at controlling virus levels, but at the same time contribute to lung pathology.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Cell Lineage
Cell Survival
Disease Models, Animal
Fibroblasts / immunology
Fibroblasts / pathology
Fibroblasts / virology
Influenza A Virus, H1N1 Subtype / genetics
Influenza A Virus, H1N1 Subtype / pathogenicity*
Influenza A Virus, H1N1 Subtype / physiology*
Integrases / genetics
Lung / immunology
Lung / pathology
Lung / virology
Mice
Mice, Inbred C57BL
Mice, Transgenic
Molecular Sequence Data
Orthomyxoviridae Infections / genetics
Orthomyxoviridae Infections / immunology
Orthomyxoviridae Infections / virology
RNA, Messenger / genetics
RNA, Viral / genetics
Recombination, Genetic

Substances

RNA, Messenger
RNA, Viral
Cre recombinase
Integrases

Associated data

GEO/GSM1422381
GEO/GSM1422382
GEO/GSM1422383
GEO/GSM1422384
GEO/GSM1422385
GEO/GSM1422386
GEO/GSM1422387
GEO/GSM1422388
GEO/GSM1422389

Abstract

Publication types

MeSH terms

Substances

Associated data

Grants and funding