Interleukin-27 Inhibition of Pandemic Influenza A Virus Infection in Human Macrophages Partially Relies on Type I IFNs.

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Amsden, Heather
Interleukin-27 , Influenza , Interferons , Viral immunology , Infection , Antiviral immunity
Zoonotic reservoirs as well as high mutation rates make influenza A viruses (IAV) a looming pandemic threat. Recent studies have identified antiviral activities of the cytokine interleukin-27 (IL-27) against several viruses, including seasonal IAV. However, the role of IL-27 during infection with pandemic IAV strains is currently unknown. Here, we demonstrated that IL-27 inhibited pandemic IAV infection (A/New York/18/2009) by type I interferon (IFN)-dependent and -independent pathways. Using THP-1-derived human macrophages, IL-27 treatment was found to dose-dependently inhibit pandemic IAV infection, and this inhibition was associated with increased expression of antiviral genes, such as myxovirus resistance 1 (MX1), radical S-adenosyl methionine domain containing 2 (RSAD2), interferon induced transmembrane protein 3 (IFITM3) and interferon regulatory factor 1 (IRF1). IL-27-mediated upregulation of these antiviral genes was partly reliant on type I IFNs; MX1 and RSAD2 expression was type I IFN-dependent, IFITM3 expression was both type I IFN-dependent and independent, and IRF1 expression was type I IFN-independent. Accordingly, IL-27 inhibition of pandemic IAV infection was reduced, but not completely abrogated, in the absence of type I IFN signaling. Furthermore, IL-27 treatment promoted the production of chemokines important for recruitment of leukocytes, particularly CXCL9 and CXCL10. These findings identify a potential protective role of IL-27 in innate immune responses to pandemic IAV infection and highlight the antiviral therapeutic potential of IL-27.
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