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Immunity. 2017 May 16;46(5):875-890.e6. doi: 10.1016/j.immuni.2017.04.025.
Interferon-λ Mediates Non-redundant Front-Line Antiviral Protection against Influenza Virus Infection without Compromising Host Fitness.
Galani IE1, Triantafyllia V1, Eleminiadou EE1, Koltsida O1, Stavropoulos A1, Manioudaki M1, Thanos D2, Doyle SE3, Kotenko SV4, Thanopoulou K1, Andreakos E5.
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Abstract
Lambda interferons (IFNλs) or type III IFNs share homology, expression patterns, signaling cascades, and antiviral functions with type I IFNs. This has complicated the unwinding of their unique non-redundant roles. Through the systematic study of influenza virus infection in mice, we herein show that IFNλs are the first IFNs produced that act at the epithelial barrier to suppress initial viral spread without activating inflammation. If infection progresses, type I IFNs come into play to enhance viral resistance and induce pro-inflammatory responses essential for confronting infection but causing immunopathology. Central to this are neutrophils which respond to both cytokines to upregulate 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-IFNλ potently suppresses these effects. IFNλs therefore constitute the front line of antiviral defense in the lung without compromising host fitness.
Copyright ? 2017 Elsevier Inc. All rights reserved.
PMID: 28514692 DOI: 10.1016/j.immuni.2017.04.025
Interferon-λ Mediates Non-redundant Front-Line Antiviral Protection against Influenza Virus Infection without Compromising Host Fitness.
Galani IE1, Triantafyllia V1, Eleminiadou EE1, Koltsida O1, Stavropoulos A1, Manioudaki M1, Thanos D2, Doyle SE3, Kotenko SV4, Thanopoulou K1, Andreakos E5.
Author information
Abstract
Lambda interferons (IFNλs) or type III IFNs share homology, expression patterns, signaling cascades, and antiviral functions with type I IFNs. This has complicated the unwinding of their unique non-redundant roles. Through the systematic study of influenza virus infection in mice, we herein show that IFNλs are the first IFNs produced that act at the epithelial barrier to suppress initial viral spread without activating inflammation. If infection progresses, type I IFNs come into play to enhance viral resistance and induce pro-inflammatory responses essential for confronting infection but causing immunopathology. Central to this are neutrophils which respond to both cytokines to upregulate 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-IFNλ potently suppresses these effects. IFNλs therefore constitute the front line of antiviral defense in the lung without compromising host fitness.
Copyright ? 2017 Elsevier Inc. All rights reserved.
PMID: 28514692 DOI: 10.1016/j.immuni.2017.04.025
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