Biomedical Ίδρυμα Ιατροβιολογικών Ερευνών, Ακαδημίας ΑθηνώνΑκαδημία Αθηνών
Επιστημονικά Επιτεύγματα :Interferon-λ Mediates Non-redundant Front-Line Antiviral Protection against Influenza Virus Infection without Compromising Host Fitness





A new paper by Evangelos Andreakos and colleagues was recently published in Immunity.  A commentary followed from the same issue of Immunity, and the article was also featured in Nature Reviews Immunology – Highlights.




Brief Overview of Publication

Textbooks state that type I IFNs constitute the primary initial defense mechanism against viral infection by inducing hundreds of genes mediating antimicrobial defenses and conferring viral resistance to neighboring cells. In the respiratory track, type I IFNs are essential for antiviral protection as their absence in IFNar1-/- mice severely impairs their ability to deal with infection. Yet, more recently a newer class of IFNs termed lambda IFNs (IFNs) or type III IFNs has been described that shares homology, expression patterns, signaling cascades and antiviral functions with type I IFNs but whose role in viral infections remains poorly characterized.

Evangelos Andreakos, Ioanna Galani and colleagues now show that IFNs are the first IFNs produced that act at the epithelial barrier to suppress initial viral spread without activating inflammation.If infection escapes IFN control, type I IFNs come into play to enhance viral resistance and induce pro-inflammatory responses essential for confronting infection but also causing immunopathology. Neutrophils are central to this process as they respond to both cytokines to up-regulate antimicrobial functions but exhibit pro-inflammatory activation only to type I IFNs. Accordingly, Ifnlr1-/- mice display enhanced type I IFN production, neutrophilia, lung injury and lethality, while therapeutic administration of PEG-. IFN potently suppresses these effects. IFNs therefore constitute the front line of antiviral defense in the lung, preceding that of type I IFNs, without compromising host fitness.




Galani IE, Triantafyllia V, Eleminiadou EE, Koltsida O, Stavropoulos A, Manioudaki M, Thanos D, Doyle SE, Kotenko SV, Thanopoulou K, Andreakos E. Interferon-λ Mediates Non-redundant Front-Line Antiviral Protection against Influenza Virus Infection without Compromising Host Fitness. Immunity. 2017 May 16;46(5):875-890.e6. doi: 10.1016/j.immuni.2017.04.025.