Diverse intracellular pathogens activate type III interferon expression from peroxisomes

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Benzimidazoles / pharmacology
  • Cell Differentiation
  • Cell Line
  • Cyclohexanes / pharmacology
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases / immunology
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Immunity, Innate*
  • Interferons / biosynthesis
  • Interferons / immunology*
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / immunology
  • Janus Kinase 2 / antagonists & inhibitors
  • Janus Kinase 2 / genetics
  • Mice
  • Peroxisomes / immunology*
  • Pyridones / pharmacology
  • RNA Interference
  • RNA, Small Interfering
  • Reoviridae / immunology
  • Reoviridae Infections / immunology
  • STAT1 Transcription Factor / antagonists & inhibitors
  • STAT1 Transcription Factor / immunology
  • Signal Transduction / immunology
  • Tyrphostins / pharmacology
  • Vidarabine / analogs & derivatives
  • Vidarabine / pharmacology
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / genetics

Substances

  • 1,2,3,4,5,6-hexabromocyclohexane
  • 2-tert-butyl-9-fluoro-3,6-dihydro-7H-benz(h)imidazo(4,5-f)isoquinoline-7-one
  • Antineoplastic Agents
  • Benzimidazoles
  • Cyclohexanes
  • Enzyme Inhibitors
  • Pyridones
  • RNA, Small Interfering
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Tyrphostins
  • alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide
  • Interferons
  • JAK2 protein, human
  • Janus Kinase 2
  • p38 Mitogen-Activated Protein Kinases
  • DDX58 protein, human
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases
  • Vidarabine
  • fludarabine

Associated data

  • GEO/GSE56783