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. Author manuscript; available in PMC: 2018 May 29.
Published in final edited form as: Immunol Rev. 2013 Sep;255(1):25–39. doi: 10.1111/imr.12101

Figure 4. Two-step induction of type I and type III IFNs.

Figure 4

, Upregulation of IFN mRNA synthesis requires the availability of activated NF-κB and IRFs. When an epithelial cell or fibroblast is infected by virus, RLRs activate NF-κB and IRF3, which then move into the nucleus and upregulate IFN-β and IFN-λ1 transcription. These ligands are then secreted from the basolateral surface of the cell. IFNAR and IFNLR on adjacent cells bind secreted IFNs, leading to synthesis of ISGs including IRF7. The availability of IRF7 allows amplification of the IFN response when infection of the IFN-exposed cell triggers its activation, translocation, dimerization, and IFN promoter binding. Although IFN-α synthesis by fibroblasts (which lack the IFNLR) requires prior IFN-β synthesis (or IFN-α/β treatment), this is not true for IFN-λ responsive epithelial cells. In the absence of IRF3 activation and IFN-β production, alternative pathways allow IFN-λ induction in the absence of IRF3 activation.