Type III interferons disrupt the lung epithelial barrier upon viral recognition
| Autor: | Maria De Santis, Nicasio Mancini, Achille Broggi, Fabio Balzarini, Roberto Spreafico, Francesca Granucci, Nicola Clementi, Ivan Zanoni, Antonino Lo Cascio, Benedetta Sposito, Sreya Ghosh |
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| Přispěvatelé: | Broggi, A, Ghosh, S, Sposito, B, Spreafico, R, Balzarini, F, Lo Cascio, A, Clementi, N, De Santis, M, Mancini, N, Granucci, F, Zanoni, I, Broggi, Achille, Ghosh, Sreya, Sposito, Benedetta, Spreafico, Roberto, Balzarini, Fabio, Lo Cascio, Antonino, Clementi, Nicola, De Santis, Maria, Mancini, Nicasio, Granucci, Francesca, Zanoni, Ivan |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Middle East respiratory syndrome coronavirus viruses Immunology Orthomyxoviridae Biology medicine.disease_cause Virus Pathogenesis 03 medical and health sciences 0302 clinical medicine Immune system Interferon Report medicine 030304 developmental biology Coronavirus 0303 health sciences Multidisciplinary Innate immune system Lung Respiratory tract infections business.industry 030306 microbiology biology.organism_classification 3. Good health interferons 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis business Viral load Reports medicine.drug |
| Zdroj: | Science (New York, N.y.) |
| Popis: | Interferons interfere with lung repair 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 , p. 712 , p. 718 ; see also p. 626 |
| Databáze: | OpenAIRE |
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