Type III interferons disrupt the lung epithelial barrier upon viral recognition

doi:10.1126/science.abc3545

GSTDTAP > 气候变化

DOI	10.1126/science.abc3545
	Type III interferons disrupt the lung epithelial barrier upon viral recognition
	Achille Broggi; Sreya Ghosh; Benedetta Sposito; Roberto Spreafico; Fabio Balzarini; Antonino Lo Cascio; Nicola Clementi; Maria De Santis; Nicasio Mancini; Francesca Granucci; Ivan Zanoni
	2020-08-07
发表期刊	Science
出版年	2020
英文摘要	Interferons (IFNs) are central to antiviral immunity. Viral recognition elicits IFN production, which in turn triggers the transcription of IFN-stimulated genes (ISGs), which engage in various antiviral functions. Type I IFNs (IFN-α and IFN-β) are widely expressed and can result in immunopathology during viral infections. By contrast, type III IFN (IFN-λ) responses are primarily restricted to mucosal surfaces and are thought to confer antiviral protection without driving damaging proinflammatory responses. Accordingly, IFN-λ has been proposed as a therapeutic in coronavirus disease 2019 (COVID-19) and other such viral respiratory diseases (see the Perspective by Grajales-Reyes and Colonna). Broggi et al. report that COVID-19 patient morbidity correlates with the high expression of type I and III IFNs in the lung. Furthermore, IFN-λ secreted by dendritic cells in the lungs of mice exposed to synthetic viral RNA causes damage to the lung epithelium, which increases susceptibility to lethal bacterial superinfections. Similarly, using a mouse model of influenza infection, Major et al. found that IFN signaling (especially IFN-λ) hampers lung repair by inducing p53 and inhibiting epithelial proliferation and differentiation. Complicating this picture, Hadjadj et al. observed that peripheral blood immune cells from severe and critical COVID-19 patients have diminished type I IFN and enhanced proinflammatory interleukin-6– and tumor necrosis factor-α–fueled responses. This suggests that in contrast to local production, systemic production of IFNs may be beneficial. The results of this trio of studies suggest that the location, timing, and duration of IFN exposure are critical parameters underlying the success or failure of therapeutics for viral respiratory infections. Science , this issue p. [706][1], p. [712][2], p. [718][3]; see also p. [626][4] Viral infections of the lower respiratory tract are a leading cause of mortality. Mounting evidence indicates that most severe cases are characterized by aberrant immune responses and do not depend on viral burden. In this study, we assessed how type III interferons (IFN-λ) contribute to the pathogenesis induced by RNA viruses. We report that IFN-λ is present in the lower, but not upper, airways of patients with coronavirus disease 2019 (COVID-19). In mice, we demonstrate that IFN-λ produced by lung dendritic cells in response to a synthetic viral RNA induces barrier damage, causing susceptibility to lethal bacterial superinfections. These findings provide a strong rationale for rethinking the pathophysiological role of IFN-λ and its possible use in clinical practice against endemic viruses, such as influenza virus as well as the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. [1]: /lookup/doi/10.1126/science.abc3545 [2]: /lookup/doi/10.1126/science.abc2061 [3]: /lookup/doi/10.1126/science.abc6027 [4]: /lookup/doi/10.1126/science.abd2208
领域	气候变化 ; 资源环境
URL	查看原文
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/288021
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Achille Broggi,Sreya Ghosh,Benedetta Sposito,et al. Type III interferons disrupt the lung epithelial barrier upon viral recognition[J]. Science,2020.
APA	Achille Broggi.,Sreya Ghosh.,Benedetta Sposito.,Roberto Spreafico.,Fabio Balzarini.,...&Ivan Zanoni.(2020).Type III interferons disrupt the lung epithelial barrier upon viral recognition.Science.
MLA	Achille Broggi,et al."Type III interferons disrupt the lung epithelial barrier upon viral recognition".Science (2020).