Type I and Type III Interferons Drive Redundant Amplification Loops to Induce a Transcriptional Signature in Influenza-Infected Airway Epithelia

• DOI: 10.1371/journal.ppat.1003773
• Publication Date: 2013-11-21T22:24:42Z
• Authors: Stefania Crotta; Sophia Davidson; Tanel Mahlakoiv; Christophe J. Desmet; Matthew R. Buckwa...; Matthew L. Albert; Peter Staeheli; Andreas Wack
• Keywords: IRF3; IRF7; Interferon type I; RIG-I

Interferons (IFNs) are a group of cytokines with well-established antiviral function. They can be induced by viral infection, secreted and bind to specific receptors on the same or neighbouring cells activate expression hundreds IFN stimulated genes (ISGs) Type I has been known for more than half century. However, recently, type III (IFNλ, IL-28/29) was shown play similar role particularly important at epithelial surfaces. Here we show that airway epithelia, primary target influenza A virus, produce both upon induction depends RIG-I/MAVS pathway. While IRF3 is generally regarded as transcription factor required initiation so-called “priming loop”, find deficiency little impact expression. In contrast, lack IRF7 reduced production significantly, only IRF3−/−IRF7−/− double completely abolished it. The transcriptional response infection largely dependent IFNs, it few upregulated in epithelia lacking (IFNAR1−/−IL-28Rα−/−). Wild-type deficient either receptor exhibit profiles indicating none selectively one system. chimeric mice, signalling stromal compartment alone significantly increased susceptibility infection. conclusion, virus induces, via RIG-I/MAVS/IRF7 pathway, IFNs which drive two overlapping redundant amplification loops upregulate ISGs protect from