title: Impacts of allergic airway inflammation on lung pathology in a mouse model of influenza A virus infection.
abstract: Influenza A virus is the respiratory pathogen responsible for influenza. Infection by the 2009 pandemic influenza A (H1N1) virus caused severe lower airway inflammation and pneumonia. Asthma is a chronic inflammatory disorder of the airways that affects the entire brachial tree, and was one of the commonest underlying medical conditions among patients hospitalized with the 2009 pandemic influenza virus infection. Although respiratory virus infections are the major causes of asthma exacerbation, the mechanism by which influenza exacerbates asthma is poorly understood. Animal models of disease comorbidity are crucial to understanding host-pathogen interactions and elucidating complex pathologies. Existing murine models of influenza virus infection in asthmatics show that asthmatic mice are highly resistant to influenza virus infection, which contradicts clinical observations in humans. Here, we developed a murine model of influenza virus/asthma comorbidity using NC/Nga mice, which are highly sensitive to allergic reactions such as atopic dermatitis and allergic airway inflammation. This model was then used to examine the impact of allergic airway inflammation on lung pathology in the 2009 pandemic influenza virus infected mice. The results showed that induction of acute allergic airway inflammation in pre-existing influenza virus infection had additive effects on exacerbation of lung pathology, which mirrors findings in human epidemiological studies. In contrast, pre-existing allergic airway inflammation protected from subsequent influenza virus infection, which was compatible with those of previous murine models of influenza virus infection in asthmatic mice. These variable outcomes of this murine model indicate that the temporal relation between allergic airway inflammation and influenza virus infection might play a critical role in asthma and influenza comorbidity. Thus, this murine model will further our understanding of how influenza virus infection affects an asthmatic host and may aid the development of strategies to improve treatments and outcomes for asthmatics harboring influenza virus infection.
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, Shinjuku, Tokyo, Japan.|Center for Influenza Virus Research, National Institute of Infectious Diseases, Musashimurayama, Tokyo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kawaguchi
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, Shinjuku, Tokyo, Japan.
authors.forename: Tadaki
authors.identifier: http://orcid.org/0000-0002-3820-9542
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, Shinjuku, Tokyo, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ohara
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, Shinjuku, Tokyo, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, Shinjuku, Tokyo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, Shinjuku, Tokyo, Japan.|Center for Influenza Virus Research, National Institute of Infectious Diseases, Musashimurayama, Tokyo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Ainai
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, Shinjuku, Tokyo, Japan.
authors.forename: Noriyo
authors.initials: N
authors.lastname: Nagata
authors.affiliation: Center for Influenza Virus Research, National Institute of Infectious Diseases, Musashimurayama, Tokyo, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Tashiro
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, Shinjuku, Tokyo, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Hasegawa
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006967:Hypersensitivity / Q000276:immunology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology*; D009980:Influenza A virus / Q000276:immunology* / Q000472:pathogenicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology*
chemical_list: D018925:Chemokines; D016207:Cytokines