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

被引:72
作者
Heaton, Nicholas S. [1 ]
Langlois, Ryan A. [1 ,2 ]
Sachs, David [3 ]
Lim, Jean K. [1 ]
Palese, Peter [1 ]
tenOever, Benjamin R. [1 ,2 ]
机构
[1] Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA
[2] Icahn Sch Med Mt Sinai, Global Hlth & Emerging Pathogens Inst, New York, NY 10029 USA
[3] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA
关键词
SURFACTANT PROTEIN-C; GENE-EXPRESSION; CLARA CELL; IN-VIVO; IMMUNE-RESPONSES; INNATE IMMUNITY; T-CELLS; LUNG; CYTOKINE; LINES;
D O I
10.1084/jem.20140488
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:1707 / 1714
页数:8
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