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. Author manuscript; available in PMC: 2012 Dec 1.
Published in final edited form as: Curr Opin Virol. 2011 Dec 1;1(6):476–486. doi: 10.1016/j.coviro.2011.11.001

Figure 2. Tissue-specific biological effects of type I and III IFN.

Figure 2

IFN-α, -β and -λ are induced by virus infection and secreted by both infected cells and plasmacytoid DCs. Their relative ratio may vary with the pathogen, but IFN-λ is the predominant cytokine secreted by either cell type in the course of influenza virus infection. IFNs can be detected in the blood and in bronchoalveolar lavage fluid during respiratory infection. Respiratory and intestinal epithelial cells are polarized, and there is evidence that IFN receptor expression on intestinal epithelia is polarized as well, with IFNAR localized to basolateral surfaces and IFNLR present on both basolateral and apical surfaces. Receptors on the basolateral surface can detect IFNs present in blood, while apical receptors will see IFNs present at the luminal surface. Signaling through IFNAR or the IFN-λ receptor leads to Stat1 and Stat2 tyrosine phosphorylation, and formation of the ISGF3 complex consisting of phospho-Stat1, phospho-Stat2 and IRF9, which activates target gene expression following nuclear translocation. T and NK cells lack the IFNLR chain, and therefore cannot respond to IFN-λ. However, the response to signaling through IFNAR is conditional (see also Fig. 3). In naïve mice, both Stat1 and Stat4 are present in NK and T cells, with constitutive levels of Stat1 much lower than Stat4. In this state, IFN-α/β signaling results predominantly in Stat4 phosphorylation, which occurs in a Stat2 independent manner and triggers IFN-γ production. In the course of viral infection, Stat1 levels are induced by IFN signaling, altering the ratio of Stat1 to Stat4 in stimulated cells. The consequences of this shift are only partly understood, but serve to explain seemingly contradictory responses of T and NK cells to IFN-α treatment. For example, despite the known antiproliferative effect of IFN-α, virus specific CD8 T cell expansion can occur at a time when IFN levels are high. However, low levels of Stat1 in actively dividing CD8 T cells from infected mice render this population resistant to the anti-proliferative effects of IFN.