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

Mahlakoiv, T., Hernandez, P., Gronke, K., Diefenbach, A., & Staeheli, P. (2015). Leukocyte-Derived IFN-α/β and Epithelial IFN-λ Constitute a Compartmentalized Mucosal Defense System that Restricts Enteric Virus Infections. PLoS Pathogens, 11, e1004782. doi:doi: 10.1371/journal.ppat.1004782.

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 Creators:
Mahlakoiv, Tanel1, 2, Author
Hernandez, Pedro3, 4, 5, Author
Gronke, Konrad2, 3, 4, Author
Diefenbach, Andreas3, 5, Author
Staeheli, Peter1, Author
Affiliations:
1Institute of Virology, University Medical Center Freiburg, Freiburg, Germany, ou_persistent22              
2Spemann Graduate School of Biology and Medicine (SGBM) Albert Ludwigs University Freiburg, Freiburg, Germany, ou_persistent22              
3Institute of Medical Microbiology and Hygiene, University Medical Center Freiburg, Freiburg, Germany, ou_persistent22              
4Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, 79108 Freiburg, DE, ou_2243640              
5Research Centre Immunology and Institute of medical microbiology and Hygiene, University of Mainz Medical Centre, Mainz, Germany, ou_persistent22              

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 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/β) and type III (IFN-λ) interferons. All nucleated cells are believed to respond to IFN-α/β, 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/β receptors. Accordingly, after oral infection of IFN-α/β 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/β 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/β system which would induce exacerbated inflammation.

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Language(s): eng - English
 Dates: 2015-04-07
 Publication Status: Published in print
 Pages: 19
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: doi: 10.1371/journal.ppat.1004782
 Degree: -

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Title: PLoS Pathogens
  Other : PLoS Pathog.
Source Genre: Journal
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Publ. Info: San Francisco, CA : Public Library of Science
Pages: 19 Volume / Issue: 11 Sequence Number: - Start / End Page: e1004782 Identifier: Other: 1000000000018830
ISSN: 1553-7366
CoNE: https://pure.mpg.de/cone/journals/resource/1000000000018830