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.
Highlights
Influenza A virus is the etiological agent of influenza, which is characterized by sudden onset of high fever and respiratory symptoms such as cough and sore throat, as well as by systemic symptoms such as headache, muscle aches, and fatigue
Among the patients with the 2009 pandemic influenza virus infection, it was noted that asthma was the most common comorbidity among patients hospitalized with influenza during this pandemic [3] [4]
Significant increases in total cell numbers and the proportion of eosinophils, which are involved in acute allergic airway inflammation, were observed in the bronchoalveolar lavage fluid (BALF) from pH1N1/OVA mice at Day 3 post-infection when compared with those in the BALF from pH1N1/PBS mice (Fig 1E), and observed in the BALF from Mock/OVA mice when compared with those in the BALF from Mock/PBS mice (Fig 1F) By contrast, the difference between the proportions of neutrophils, which is triggered by influenza virus infection, in these mice was not significant (Fig 1E)
Summary
Influenza A virus is the etiological agent of influenza, which is characterized by sudden onset of high fever and respiratory symptoms such as cough and sore throat, as well as by systemic symptoms such as headache, muscle aches, and fatigue. Influenza viruses continually circulate in human populations worldwide. Annual epidemics result in approximately three to five million cases of severe illness and approximately 250,000 to 500,000 deaths [1]. The influenza pandemic of 2009 was caused by a novel triple reassortant influenza virus, A(H1N1)pdm2009, which first emerged in pigs in Mexico but spread rapidly across the globe [2]. The pandemic influenza occasionally caused severe lower airway inflammation and pneumonia. Among the patients with the 2009 pandemic influenza virus infection, it was noted that asthma was the most common comorbidity among patients hospitalized with influenza during this pandemic [3] [4]
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