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Review
. 2020;12(6):437-447.
doi: 10.1159/000508379. Epub 2020 Jun 19.

The Role of Type I IFNs in Influenza: Antiviral Superheroes or Immunopathogenic Villains?

Wenxin Wu  1 , Jordan P Metcalf  2   3   4
Affiliations
Review

The Role of Type I IFNs in Influenza: Antiviral Superheroes or Immunopathogenic Villains?

Wenxin Wu et al. J Innate Immun. 2020.

Abstract

The important role of interferons (IFNs) in antiviral innate immune defense is well established. Although recombinant IFN-α was approved for cancer and chronic viral infection treatment by regulatory agencies in many countries starting in 1986, no IFNs are approved for treatment of influenza A virus (IAV) infection. This is partially due to the complex effects of IFNs in acute influenza infection. IAV attacks the human respiratory system and causes significant morbidity and mortality globally. During influenza infection, depending on the strain of IAV and the individual host, type I IFNs can have protective antiviral effects or can contribute to immunopathology. In the context of virus infection, the immune system has complicated mechanisms regulating the expression and effects of type I IFN to maximize the antiviral response by both activating and enhancing beneficial innate cell function, while limiting immunopathological responses that lead to exaggerated tissue damage. In this review, we summarize the complicated, but important, role of type I IFNs in influenza infections. This includes both protective and harmful effects of these important cytokines during infection.

Keywords: Cytokines; Influenza; Innate immunity; Interferon; Viral infection.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Fig. 1
Fig. 1
Induction of type I IFNs and ISGs by influenza virus. Innate immune cells, such as macrophages and lung epithelial cells, produce type I IFNs after sensing IAV genomic RNA using various PRRs. In infected and neighboring cells, type I IFN signaling activates the JAK-STAT pathway, leading to transcription of ISGs, the products of which initiate intracellular antiviral effectors that limit the spread of the viruses. IFN, interferon; ISG, IFN-stimulated gene; PRR, pattern recognition receptor; JAK, Janus kinase; STAT, signal transducer and activator of transcription; TLR, Toll-like receptor; RLR, RIG-I like helicase; NLR, nucleotide-binding domain and leucine-rich-repeat-containing protein.
Fig. 2
Fig. 2
Type I IFNs modulate immune cell functions during influenza virus infection. IFN, interferon; NK cell, natural killer cell; DC, dendritic cell; IFNAR, IFN-α/β receptor.
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