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Published online August 10, 2009
The Journal of Immunology, 2009, 183, 3229 -3236
Copyright © 2009 by The American Association of Immunologists, Inc.
doi:10.4049/jimmunol.0804277

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Novel Reporter Mouse Reveals Constitutive and Inflammatory Expression of IFN-β In Vivo1

Stefan Lienenklaus2,*, Marius Cornitescu{dagger}, Natalia Zietara*, Marcin Lyszkiewicz*, Nelson Gekara*, Jadwiga Jablonska*, Frank Edenhofer{ddagger}, Klaus Rajewsky§, Dunja Bruder, Martin Hafner||, Peter Staeheli{dagger} and Siegfried Weiss*

* Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany; {dagger} Department of Virology, University of Freiburg, Freiburg, Germany; {ddagger} Stem Cell Engineering Group, University of Bonn, Bonn, Germany; § Immune Disease Institute, Harvard Medical School, Boston, MA 02115; Immunoregulation, Helmholtz Centre for Infection Research, Braunschweig, Germany; and || Institute for Genetics, University of Cologne, Cologne, Germany

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-β 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-β gene induction in vivo. Using this reporter mouse, we reveal strong tissue-specific induction of IFN-β following infection with influenza or La Crosse virus. Importantly, this reporter mouse also allowed us to visualize that IFN-β 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-β under noninflammatory conditions. This relatively high constitutive expression was controlled by the NF Aire and might influence induction of tolerance or T cell development.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was supported in part by the German Research Council (DFG), the EC via Clinigene and the Marie Curie Action Miditrain MEST-CT-2004–504990, the Helmholtz Gemeinschaft via Helmholtz International Research School for Infection Biology, the Deutsche Krebshilfe, and the Kultusministerium of Niedersachsen via the Lichtenberg PhD program.

2 Address correspondence and reprint requests to Dr. Stefan Lienenklaus, Molecular Immunology, Helmholtz Centre for Infection Research, Inhoffenstr. 7, Braunschweig, Germany. E-mail address: stl{at}gbf.de

3 Abbreviations used in this paper: ES, embryonic stem; NDV, Newcastle disease virus; wt, wild type; LACV, La Crosse virus; DC, dendritic cell.

4 The online version of this article contains supplementary material.




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G. Kochs, L. Martinez-Sobrido, S. Lienenklaus, S. Weiss, A. Garcia-Sastre, and P. Staeheli
Strong interferon-inducing capacity of a highly virulent variant of influenza A virus strain PR8 with deletions in the NS1 gene
J. Gen. Virol., December 1, 2009; 90(12): 2990 - 2994.
[Abstract] [Full Text] [PDF]




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