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Nat Immunol. 2014 Aug;15(8):717-26. doi: 10.1038/ni.2915. Epub 2014 Jun 22.

Diverse intracellular pathogens activate type III interferon expression from peroxisomes.

Author information

1
Harvard Medical School and Division of Gastroenterology, Boston Children's Hospital, Boston, Massachusetts, USA.
2
1] Harvard Medical School and Division of Gastroenterology, Boston Children's Hospital, Boston, Massachusetts, USA. [2].
3
1] Institut Pasteur, Unité des Interactions Bactéries Cellules, Institut National de la Santé et de la Recherche Médicale U604, Institut national de la recherche agronomique (INRA) USC2020, Paris, France. [2].
4
1] Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA. [2] Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
5
Department of Infectious Diseases, Virology Schaller research group at CellNetworks and Deutsches Krebsforschungszentrum (DKFZ), University of Heidelberg, Heidelberg, Germany.
6
Institut Pasteur, Unité des Interactions Bactéries Cellules, Institut National de la Santé et de la Recherche Médicale U604, Institut national de la recherche agronomique (INRA) USC2020, Paris, France.

Abstract

Type I interferon responses are considered the primary means by which viral infections are controlled in mammals. Despite this view, several pathogens activate antiviral responses in the absence of type I interferons. The mechanisms controlling type I interferon-independent responses are undefined. We found that RIG-I like receptors (RLRs) induce type III interferon expression in a variety of human cell types, and identified factors that differentially regulate expression of type I and type III interferons. We identified peroxisomes as a primary site of initiation of type III interferon expression, and revealed that the process of intestinal epithelial cell differentiation upregulates peroxisome biogenesis and promotes robust type III interferon responses in human cells. These findings highlight the importance of different intracellular organelles in specific innate immune responses.

PMID:
24952503
PMCID:
PMC4106986
DOI:
10.1038/ni.2915
[Indexed for MEDLINE]
Free PMC Article

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