| First Author | Mahlakõiv T | Year | 2015 |
| Journal | PLoS Pathog | Volume | 11 |
| Issue | 4 | Pages | e1004782 |
| PubMed ID | 25849543 | Mgi Jnum | J:248110 |
| Mgi Id | MGI:5917569 | Doi | 10.1371/journal.ppat.1004782 |
| Citation | Mahlakoiv T, et al. (2015) Leukocyte-derived IFN-alpha/beta and epithelial IFN-lambda constitute a compartmentalized mucosal defense system that restricts enteric virus infections. PLoS Pathog 11(4):e1004782 |
| abstractText | 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-alpha/beta) and type III (IFN-lambda) interferons. All nucleated cells are believed to respond to IFN-alpha/beta, whereas IFN-lambda 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-alpha/beta receptors. Accordingly, after oral infection of IFN-alpha/beta 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-lambda receptor-deficient mice, suggesting that the gut mucosa is equipped with a compartmentalized IFN system in which epithelial cells mainly respond to IFN-lambda that they produce after viral infection, whereas other cells of the gut mostly rely on IFN-alpha/beta for antiviral defense. In suckling mice with IFN-lambda receptor deficiency, reovirus replicated in the gut epithelium and additionally infected epithelial cells lining the bile ducts, indicating that infants may use IFN-lambda for the control of virus infections in various epithelia-rich tissues. Thus, IFN-lambda 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-alpha/beta system which would induce exacerbated inflammation. |
