IFNλ is a potent anti-influenza therapeutic without the inflammatory side effects of IFNα treatment.

Autor: Davidson S; Immunoregulation Laboratory, Mill Hill Laboratory, Francis Crick Institute, London, UK., McCabe TM; Immunoregulation Laboratory, Mill Hill Laboratory, Francis Crick Institute, London, UK., Crotta S; Immunoregulation Laboratory, Mill Hill Laboratory, Francis Crick Institute, London, UK., Gad HH; Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark., Hessel EM; Refractory Respiratory Inflammation Discovery Performance Unit, Respiratory Therapy Area, GSK, Stevenage, UK., Beinke S; Refractory Respiratory Inflammation Discovery Performance Unit, Respiratory Therapy Area, GSK, Stevenage, UK., Hartmann R; Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark., Wack A; Immunoregulation Laboratory, Mill Hill Laboratory, Francis Crick Institute, London, UK andreas.wack@crick.ac.uk.
Jazyk: angličtina
Zdroj: EMBO molecular medicine [EMBO Mol Med] 2016 Sep 01; Vol. 8 (9), pp. 1099-112. Date of Electronic Publication: 2016 Sep 01 (Print Publication: 2016).
DOI: 10.15252/emmm.201606413
Abstrakt: Influenza A virus (IAV)-induced severe disease is characterized by infected lung epithelia, robust inflammatory responses and acute lung injury. Since type I interferon (IFNαβ) and type III interferon (IFNλ) are potent antiviral cytokines with immunomodulatory potential, we assessed their efficacy as IAV treatments. IFNλ treatment of IAV-infected Mx1-positive mice lowered viral load and protected from disease. IFNα treatment also restricted IAV replication but exacerbated disease. IFNα treatment increased pulmonary proinflammatory cytokine secretion, innate cell recruitment and epithelial cell death, unlike IFNλ-treatment. IFNλ lacked the direct stimulatory activity of IFNα on immune cells. In epithelia, both IFNs induced antiviral genes but no inflammatory cytokines. Similarly, human airway epithelia responded to both IFNα and IFNλ by induction of antiviral genes but not of cytokines, while hPBMCs responded only to IFNα. The restriction of both IFNλ responsiveness and productive IAV replication to pulmonary epithelia allows IFNλ to limit IAV spread through antiviral gene induction in relevant cells without overstimulating the immune system and driving immunopathology. We propose IFNλ as a non-inflammatory and hence superior treatment option for human IAV infection.
(© 2016 The Authors. Published under the terms of the CC BY 4.0 license.)
Databáze: MEDLINE
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