The Mouse as Model System to Study Host‐Pathogen Interactions in Influenza A Infections

Wilk, Esther; Schughart, Klaus

doi:10.1002/9780470942390.mo110173

Cited by 19 publications

(17 citation statements)

References 71 publications

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“…Characteristics of these viruses were described previously [21]. Virus stocks were prepared by infection of 10-day-old embryonated chicken eggs as described [19]. Inbred mouse strains C57BL/6J and DBA/2J were obtained from Janvier, France and maintained under specific pathogen free conditions, according to the German animal welfare law.…”

Section: Methodsmentioning

confidence: 99%

“…Viral load in infected lungs was determined on MDCK II (Madin-Darby Canine Kidney II) cells using the FFU assay as described [19], [21]. For determination of viral load, lungs of mice were homogenized in PBS with 0.1% BSA using the Poly Tron 2100 homogenizer.…”

Section: Methodsmentioning

confidence: 99%

“…A large amount of information has been accumulated from experimental animal studies [14], [15], [16], [17], [18], [19]. However, these data were very seldom correlated with biomarkers in body fluids.…”

Section: Introductionmentioning

confidence: 99%

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Cellular Changes in Blood Indicate Severe Respiratory Disease during Influenza Infections in Mice

et al. 2014

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Influenza A infection is a serious threat to human and animal health. Many of the biological mechanisms of the host-pathogen-interactions are still not well understood and reliable biomarkers indicating the course of the disease are missing. The mouse is a valuable model system enabling us to study the local inflammatory host response and the influence on blood parameters under controlled circumstances. Here, we compared the lung and peripheral changes after PR8 (H1N1) influenza A virus infection in C57BL/6J and DBA/2J mice using virus variants of different pathogenicity resulting in non-lethal and lethal disease. We monitored hematological and immunological parameters revealing that the granulocyte to lymphocyte ratio in the blood represents an early indicator of severe disease progression already two days after influenza A infection in mice. These findings might be relevant to optimize early diagnostic options of severe influenza disease and to monitor successful therapeutic treatment in humans.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Cellular Changes in Blood Indicate Severe Respiratory Disease during Influenza Infections in Mice

et al. 2014

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“…Virus stocks were prepared by infection of 10-day-old embryonated chicken eggs as described in [56]. The Ifi27l2a knock-out mouse strain (C57BL/6NTac- Ifi27l2a tm1(KOMP)Vlcg ) used for this research project was created from ES cell clone 10949A-H8, obtained from the KOMP Repository (www.komp.org)).…”

Section: Methodsmentioning

confidence: 99%

The Interferon-Induced Gene Ifi27l2a is Active in Lung Macrophages and Lymphocytes After Influenza A Infection but Deletion of Ifi27l2a in Mice Does Not Increase Susceptibility to Infection

et al. 2014

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Interferons represent one of the first and essential host defense mechanisms after infection, and the activation of the IFN-pathway results in the transcriptional activation of hundreds of interferon-stimulated genes. The alpha-inducible protein 27 like 2A (Ifi27l2a) gene (human synonym: ISG12) is strongly up-regulated in the lung after influenza A infection in mice and has been shown in gene expression studies to be highly correlated to other activated genes. Therefore, we investigated the role of Ifi27l2a for the host defense to influenza A infections in more detail. RT-PCR analyses in non-infected mice demonstrated that Ifi27l2a was expressed in several tissues, including the lung. Detailed analyses of reporter gene expression in lungs from Ifi27l2a-LacZ mice revealed that Ifi27l2a was expressed in macrophages and lymphocytes but not in alveolar cells or bronchiolar epithelium cells. The number of macrophages and lymphocyte strongly increased in the lung after infection, but no significant increase in expression levels of the LacZ reporter gene was found within individual immune cells. Also, no reporter gene expression was found in bronchiolar epithelial cells, alveolar cells or infiltrating neutrophils after infection. Thus, up-regulation of Ifi27l2a in infected lungs is mainly due to the infiltration of macrophages and lymphocytes. Most surprisingly, deletion of Ifi27l2a in mouse knock-out lines did not result in increased susceptibility to infections with H1N1 or H7N7 influenza A virus compared to wild type C57BL/6N mice, suggesting a less important role of the gene for the host response to influenza infections than for bacterial infections.

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“…Virus stocks were propagated in the chorioallantoic cavity of 10-day-old pathogen-free embryonated chicken eggs for 48 h at 37 ° C as described previously [23] . The viral titer was determined by focus-forming unit (FFU) assay as described previously [23] . Irf7 tm1Ttg ( Irf3 -/-Irf7 -/-) DKO mice were generated by breeding Irf3 -/-with Irf7 -/-mice.…”

Section: Virus and Micementioning

confidence: 99%

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

Hatesuer

Hoang

Riese³

et al. 2016

J Innate Immun

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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.

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The Mouse as Model System to Study Host‐Pathogen Interactions in Influenza A Infections

Cited by 19 publications

References 71 publications

Cellular Changes in Blood Indicate Severe Respiratory Disease during Influenza Infections in Mice

Cellular Changes in Blood Indicate Severe Respiratory Disease during Influenza Infections in Mice

The Interferon-Induced Gene Ifi27l2a is Active in Lung Macrophages and Lymphocytes After Influenza A Infection but Deletion of Ifi27l2a in Mice Does Not Increase Susceptibility to Infection

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

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