Leukocyte-Derived IFN-α/β and Epithelial IFN-λ Constitute a Compartmentalized Mucosal Defense System that Restricts Enteric Virus Infections

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Virus-induced interferon consists of two distinct families of molecules, IFN-α/β and IFN-λ. IFN-α/β family members are key antiviral molecules that confer protection against a large number of viruses infecting a wide variety of cell types. By contrast, IFN-λ responses are largely confined to epithelial cells due to highly restricted expression of the cognate receptor. Interestingly, virus resistance of the gut epithelium is not dependent on IFN-α/β but rather relies on IFN-λ, questioning the prevailing view that receptors for IFN-α/β are expressed ubiquitously. Here we demonstrate that the IFN-α/β system is unable to compensate for IFN-λ deficiency during infections with epitheliotropic viruses because intestinal epithelial cells do not express functional receptors for IFN-α/β. We further demonstrate that virus-infected intestinal epithelial cells are potent producers of IFN-λ, indicating that the gut mucosa possesses a compartmentalized IFN system in which epithelial cells predominantly respond to IFN-λ, whereas other cells of the gut mainly rely on IFN-α/β for antiviral defense. We suggest that IFN-λ may have evolved as an autonomous virus defense system of the gut mucosa to avoid unnecessarily frequent triggering of the IFN-α/β system which, due to its potent activity on immune cells, would induce exacerbated inflammation.

Vyšlo v časopise: Leukocyte-Derived IFN-α/β and Epithelial IFN-λ Constitute a Compartmentalized Mucosal Defense System that Restricts Enteric Virus Infections. PLoS Pathog 11(4): e32767. doi:10.1371/journal.ppat.1004782
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004782

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