Leukocyte-derived IFN-α/ß and epithelial IFN-λ constitute a compartmentalized mucosal defense system that restricts enteric virus infections.
PLoS Pathog
; 11(4): e1004782, 2015 Apr.
Article
em En
| MEDLINE
| ID: mdl-25849543
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-α/ß) and type III (IFN-λ) interferons. All nucleated cells are believed to respond to IFN-α/ß, whereas IFN-λ 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-α/ß receptors. Accordingly, after oral infection of IFN-α/ß 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-λ receptor-deficient mice, suggesting that the gut mucosa is equipped with a compartmentalized IFN system in which epithelial cells mainly respond to IFN-λ that they produce after viral infection, whereas other cells of the gut mostly rely on IFN-α/ß for antiviral defense. In suckling mice with IFN-λ receptor deficiency, reovirus replicated in the gut epithelium and additionally infected epithelial cells lining the bile ducts, indicating that infants may use IFN-λ for the control of virus infections in various epithelia-rich tissues. Thus, IFN-λ 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-α/ß system which would induce exacerbated inflammation.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Infecções por Reoviridae
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Células Epiteliais
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Mucosa Intestinal
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Leucócitos
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article