Novel reporter mouse reveals constitutive and inflammatory expression of IFN-beta in vivo.
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.
Lienenklaus
Stefan
S
Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany. stl@gbf.de
Cornitescu
Marius
M
Zietara
Natalia
N
Łyszkiewicz
Marcin
M
Gekara
Nelson
N
Jabłónska
Jadwiga
J
Edenhofer
Frank
F
Rajewsky
Klaus
K
Bruder
Dunja
D
Hafner
Martin
M
Staeheli
Peter
P
Weiss
Siegfried
S
D000818:Animals; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000276:immunology / Q000473:pathology / Q000821:virology; D005260:Female; D017930:Genes, Reporter / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology*; D053126:Influenza A Virus, H7N7 Subtype / Q000235:genetics / Q000276:immunology; D016899:Interferon-beta / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics*; D018062:La Crosse virus / Q000235:genetics / Q000276:immunology; D049409:Luciferases, Firefly / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009521:Newcastle Disease / Q000235:genetics / Q000276:immunology / Q000473:pathology; D009976:Orthomyxoviridae Infections / Q000235:genetics / Q000276:immunology / Q000473:pathology; D013950:Thymus Gland / Q000276:immunology / Q000473:pathology / Q000821:virology
D018836:Inflammation Mediators; D016899:Interferon-beta; D049409:Luciferases, Firefly