Leukocyte-derived IFN-?/? and epithelial IFN-? constitute a compartmentalized mucosal defense system that restricts enteric virus infections.

ABSTRACT: Epithelial cells are a major port of entry for many viruses, but the molecular networks which protect barrier surfaces against viral infections are incompletely understood. Viral infections induce simultaneous production of type I (IFN-?/?) and type III (IFN-?) interferons. All nucleated cells are believed to respond to IFN-?/?, whereas IFN-? responses are largely confined to epithelial cells. We observed that intestinal epithelial cells, unlike hematopoietic cells of this organ, express only very low levels of functional IFN-?/? receptors. Accordingly, after oral infection of IFN-?/? receptor-deficient mice, human reovirus type 3 specifically infected cells in the lamina propria but, strikingly, did not productively replicate in gut epithelial cells. By contrast, reovirus replicated almost exclusively in gut epithelial cells of IFN-? receptor-deficient mice, suggesting that the gut mucosa is equipped with a compartmentalized IFN system in which epithelial cells mainly respond to IFN-? that they produce after viral infection, whereas other cells of the gut mostly rely on IFN-?/? for antiviral defense. In suckling mice with IFN-? receptor deficiency, reovirus replicated in the gut epithelium and additionally infected epithelial cells lining the bile ducts, indicating that infants may use IFN-? for the control of virus infections in various epithelia-rich tissues. Thus, IFN-? should be regarded as an autonomous virus defense system of the gut mucosa and other epithelial barriers that may have evolved to avoid unnecessarily frequent triggering of the IFN-?/? system which would induce exacerbated inflammation.

SUBMITTER: Mahlakoiv T 

PROVIDER: S-EPMC4388470 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature