Type I and III interferons disrupt lung epithelial repair during recovery from viral infection

doi:10.1126/science.abc2061

GSTDTAP > 气候变化

DOI	10.1126/science.abc2061
	Type I and III interferons disrupt lung epithelial repair during recovery from viral infection
	Jack Major; Stefania Crotta; Miriam Llorian; Teresa M. McCabe; Hans Henrik Gad; Simon L. Priestnall; Rune Hartmann; Andreas Wack
	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] Excessive cytokine signaling frequently exacerbates lung tissue damage during respiratory viral infection. Type I (IFN-α and IFN-β) and III (IFN-λ) interferons are host-produced antiviral cytokines. Prolonged IFN-α and IFN-β responses can lead to harmful proinflammatory effects, whereas IFN-λ mainly signals in epithelia, thereby inducing localized antiviral immunity. In this work, we show that IFN signaling interferes with lung repair during influenza recovery in mice, with IFN-λ driving these effects most potently. IFN-induced protein p53 directly reduces epithelial proliferation and differentiation, which increases disease severity and susceptibility to bacterial superinfections. Thus, excessive or prolonged IFN production aggravates viral infection by impairing lung epithelial regeneration. Timing and duration are therefore critical parameters of endogenous IFN action and should be considered carefully for IFN therapeutic strategies against viral infections such as influenza and coronavirus disease 2019 (COVID-19). [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/288024
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Jack Major,Stefania Crotta,Miriam Llorian,et al. Type I and III interferons disrupt lung epithelial repair during recovery from viral infection[J]. Science,2020.
APA	Jack Major.,Stefania Crotta.,Miriam Llorian.,Teresa M. McCabe.,Hans Henrik Gad.,...&Andreas Wack.(2020).Type I and III interferons disrupt lung epithelial repair during recovery from viral infection.Science.
MLA	Jack Major,et al."Type I and III interferons disrupt lung epithelial repair during recovery from viral infection".Science (2020).