Interferon-λ Mediates Non-redundant Front-Line Antiviral Protection against Influenza Virus Infection without Compromising Host Fitness

Immunity
Ioanna E GalaniEvangelos Andreakos

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.

Citations

Jun 28, 2017·Nature Reviews. Immunology·Kirsty Minton
Jul 20, 2017·Nature Immunology·Ioana Visan
Feb 18, 2018·Clinical and Experimental Immunology·S E JørgensenT H Mogensen
Jan 25, 2018·Viruses·Harshad IngleMegan T Baldridge
Oct 27, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Adeola A ObajemuOlusegun O Onabajo
Nov 19, 2017·Science Immunology·Daniel Schnepf, Peter Staeheli
Dec 14, 2017·Frontiers in Immunology·Ivan ZanoniAchille Broggi
May 25, 2018·ELife·Andreas Wack
Sep 6, 2018·American Journal of Respiratory Cell and Molecular Biology·Danielle AhnAlice Prince
Sep 20, 2017·Nature Immunology·Emily A HemannRam Savan
Mar 25, 2019·International Journal of Molecular Sciences·Megan L StaniferSteeve Boulant
Apr 19, 2019·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Thomas R O'BrienLudmila Prokunina-Olsson
Feb 26, 2019·Infection and Immunity·Helen E RichJohn F Alcorn
Apr 24, 2019·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Amariliz Rivera
Jun 5, 2019·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Sreedhar Chinnaswamy, Marek L Kowalski
Jun 5, 2019·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Thomas R O'Brien, Sarah S Jackson
Jun 7, 2019·Medical Microbiology and Immunology·Michelle M ThomsenTrine H Mogensen
Jun 30, 2019·European Journal of Immunology·Michelle M ThomsenTrine H Mogensen
Sep 24, 2019·Viral Immunology·Rebecca L CasazzaJonathan J Miner
Oct 8, 2017·Science Immunology·Vanessa EspinosaAmariliz Rivera
Feb 6, 2020·International Journal of Molecular Sciences·Vincent D GiacaloneRabindra Tirouvanziam
May 5, 2020·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Julian LindenPeter Staeheli
May 31, 2019·Clinical Microbiology Reviews·Jennifer A GrousdJohn F Alcorn
Apr 26, 2020·EMBO Molecular Medicine·Evangelos Andreakos, Sotirios Tsiodras
Jul 6, 2020·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·Kyle SalkaGustavo Nino
Jul 30, 2020·PLoS Pathogens·Margarida Sa RiberoSébastien Nisole
Aug 5, 2020·The Journal of Experimental Medicine·Benjamin IsraelowAkiko Iwasaki
Sep 10, 2020·American Journal of Physiology. Lung Cellular and Molecular Physiology·Su-Ling LooNathan W Bartlett
Apr 18, 2020·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Thomas R O'BrienRune Hartmann
Jul 6, 2017·The Journal of Pathology·Akrivi ChrysanthopoulouKonstantinos Ritis
Jul 26, 2018·Frontiers in Immunology·Tsz-Fung YipSuki Man-Yan Lee
Sep 27, 2018·Frontiers in Immunology·Sophia Davidson
Jun 16, 2019·Nature Reviews. Immunology·Liang YePeter Staeheli

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