Novel reporter mouse reveals constitutive and inflammatory expression of IFN-beta in vivo

J Immunol. 2009 Sep 1;183(5):3229-36. doi: 10.4049/jimmunol.0804277. Epub 2009 Aug 10.

Abstract

Type I IFN is a major player in innate and adaptive immune responses. Besides, it is involved in organogenesis and tumor development. Generally, IFN responses are amplified by an autocrine loop with IFN-beta as the priming cytokine. However, due to the lack of sensitive detection systems, where and how type I IFN is produced in vivo is still poorly understood. In this study, we describe a luciferase reporter mouse, which allows tracking of IFN-beta gene induction in vivo. Using this reporter mouse, we reveal strong tissue-specific induction of IFN-beta following infection with influenza or La Crosse virus. Importantly, this reporter mouse also allowed us to visualize that IFN-beta is expressed constitutively in several tissues. As suggested before, low amounts of constitutively produced IFN might maintain immune cells in an activated state ready for a timely response to pathogens. Interestingly, thymic epithelial cells were the major source of IFN-beta under noninflammatory conditions. This relatively high constitutive expression was controlled by the NF Aire and might influence induction of tolerance or T cell development.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Transformed
  • Cells, Cultured
  • Epithelial Cells / immunology
  • Epithelial Cells / pathology
  • Epithelial Cells / virology
  • Female
  • Genes, Reporter* / immunology
  • Inflammation Mediators / metabolism
  • Inflammation Mediators / physiology*
  • Influenza A Virus, H7N7 Subtype / genetics
  • Influenza A Virus, H7N7 Subtype / immunology
  • Interferon-beta / biosynthesis*
  • Interferon-beta / deficiency
  • Interferon-beta / genetics*
  • La Crosse virus / genetics
  • La Crosse virus / immunology
  • Luciferases, Firefly / genetics
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Newcastle Disease / genetics
  • Newcastle Disease / immunology
  • Newcastle Disease / pathology
  • Orthomyxoviridae Infections / genetics
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / pathology
  • Thymus Gland / immunology
  • Thymus Gland / pathology
  • Thymus Gland / virology

Substances

  • Inflammation Mediators
  • Interferon-beta
  • Luciferases, Firefly