Deletion of Irf3 and Irf7 Genes in Mice Results in Altered Interferon Pathway Activation and Granulocyte-Dominated Inflammatory Responses to Influenza A Infection.
The interferon (IFN) pathway plays an essential role in the innate immune response following viral infections and subsequent shaping of adaptive immunity. Infections with influenza A viruses (IAV) activate the IFN pathway after the recognition of pathogen-specific molecular patterns by respective pattern recognition receptors. The IFN regulatory factors IRF3 and IRF7 are key players in the regulation of type I and III IFN genes. In this study, we analyzed the role of IRF3 and IRF7 for the host response to IAV infections in Irf3-/-, Irf7-/-, and Irf3-/-Irf7-/- knockout mice. While the absence of IRF3 had only a moderate impact on IFN expression, deletion of IRF7 completely abolished IFNα production after infection. In contrast, lack of both IRF3 and IRF7 resulted in the absence of both IFNα and IFNβ after IAV infection. In addition, IAV infection of double knockout mice resulted in a strong increase of mortality associated with a massive influx of granulocytes in the lung and reduced activation of the adaptive immune response.
Department of Infection Genetics, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Bastian
B
Hatesuer
Hang Thi Thu
HT
Hoang
Peggy
P
Riese
Stephanie
S
Trittel
Ingo
I
Gerhauser
Husni
H
Elbahesh
Robert
R
Geffers
Esther
E
Wilk
Klaus
K
Schughart
D056704:Adaptive Immunity; D000818:Animals; D002478:Cells, Cultured; D006098:Granulocytes / Q000276:immunology* / Q000821:virology; D007249:Inflammation / Q000276:immunology*; D009980:Influenza A virus / Q000276:immunology*; D050838:Interferon Regulatory Factor-3 / Q000235:genetics / Q000378:metabolism*; D050839:Interferon Regulatory Factor-7 / Q000235:genetics / Q000378:metabolism*; D016898:Interferon-alpha / Q000378:metabolism; D008168:Lung / Q000276:immunology* / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D015398:Signal Transduction
D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; D016898:Interferon-alpha; C494233:Irf3 protein, mouse; C494235:Irf7 protein, mouse