Deletion of Irf3 and Irf7 Genes in Mice Results in Altered Interferon Pathway Activation and Granulocyte-Dominated Inflammatory Responses to Influenza A Infection

Bastian Hatesuer, Hang Thi Thu Hoang, Peggy Riese, Stephanie Trittel, Ingo Gerhauser, Husni Elbahesh, Robert Geffers, Esther Wilk, Klaus Schughart

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)145-161
Number of pages17
JournalJournal of Innate Immunity
Volume9
Issue number2
DOIs
StatePublished - Feb 1 2017

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Granulocytes
Interferons
Human Influenza
Influenza A virus
Virus Diseases
Infection
Genes
Adaptive Immunity
Knockout Mice
Interferon Regulatory Factors
Pattern Recognition Receptors
Interferon Type I
Innate Immunity
Lung
Mortality

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy

Cite this

Deletion of Irf3 and Irf7 Genes in Mice Results in Altered Interferon Pathway Activation and Granulocyte-Dominated Inflammatory Responses to Influenza A Infection. / Hatesuer, Bastian; Hoang, Hang Thi Thu; Riese, Peggy; Trittel, Stephanie; Gerhauser, Ingo; Elbahesh, Husni; Geffers, Robert; Wilk, Esther; Schughart, Klaus.

In: Journal of Innate Immunity, Vol. 9, No. 2, 01.02.2017, p. 145-161.

Research output: Contribution to journalArticle

Hatesuer, B, Hoang, HTT, Riese, P, Trittel, S, Gerhauser, I, Elbahesh, H, Geffers, R, Wilk, E & Schughart, K 2017, 'Deletion of Irf3 and Irf7 Genes in Mice Results in Altered Interferon Pathway Activation and Granulocyte-Dominated Inflammatory Responses to Influenza A Infection', Journal of Innate Immunity, vol. 9, no. 2, pp. 145-161. https://doi.org/10.1159/000450705
Hatesuer, Bastian ; Hoang, Hang Thi Thu ; Riese, Peggy ; Trittel, Stephanie ; Gerhauser, Ingo ; Elbahesh, Husni ; Geffers, Robert ; Wilk, Esther ; Schughart, Klaus. / Deletion of Irf3 and Irf7 Genes in Mice Results in Altered Interferon Pathway Activation and Granulocyte-Dominated Inflammatory Responses to Influenza A Infection. In: Journal of Innate Immunity. 2017 ; Vol. 9, No. 2. pp. 145-161.
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