Temporal and spatial resolution of type I and III interferon responses in vivo.
Although the action of interferons (IFNs) has been extensively studied in vitro, limited information is available on the spatial and temporal activation pattern of IFN-induced genes in vivo. We created BAC transgenic mice expressing firefly luciferase under transcriptional control of the Mx2 gene promoter. Expression of the reporter with regard to onset and kinetics of induction parallels that of Mx2 and is thus a hallmark for the host response. Substantial constitutive expression of the reporter gene was observed in the liver and most other tissues of transgenic mice, whereas this expression was strongly reduced in animals lacking functional type I IFN receptors. As expected, the reporter gene was induced not only in response to type I (alpha and beta) and type III (lambda) IFNs but also in response to a variety of IFN inducers such as double-stranded RNA, lipopolysaccharide (LPS), and viruses. In vivo IFN subtypes show clear differences with respect to their kinetics of action and to their spatial activation pattern: while the type I IFN response was strong in liver, spleen, and kidney, type III IFN reactivity was most prominent in organs with mucosal surfaces. Infection of reporter mice with virus strains that differ in their pathogenicity shows that the IFN response is significantly altered in the strength of IFN action at sites which are not primarily infected as well as by the onset and duration of gene induction.
Pulverer
Julia Elisabeth
JE
Department of Gene Regulation and Differentiation, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Rand
Ulfert
U
Lienenklaus
Stefan
S
Kugel
Daniela
D
Zietara
Natalia
N
Kochs
Georg
G
Naumann
Ronald
R
Weiss
Siegfried
S
Staeheli
Peter
P
Hauser
Hansjörg
H
Köster
Mario
M
D000818:Animals; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D007251:Influenza, Human / Q000235:genetics / Q000378:metabolism / Q000821:virology; D029521:Alphainfluenzavirus / Q000502:physiology; D016898:Interferon-alpha / Q000235:genetics / Q000378:metabolism*; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000737:chemistry / Q000378:metabolism; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D064547:Myxovirus Resistance Proteins; D009928:Organ Specificity; D053633:Receptor, Interferon alpha-beta / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000737:chemistry / Q000378:metabolism; D018117:Thogotovirus / Q000502:physiology; D051598:Whole Body Imaging
C508032:Ifnar1 protein, mouse; D016898:Interferon-alpha; C579067:Mx2 protein, mouse; D064547:Myxovirus Resistance Proteins; D053633:Receptor, Interferon alpha-beta; D016899:Interferon-beta; D007371:Interferon-gamma; D019204:GTP-Binding Proteins