Eosinophils residing in the airways of mice respond to influenza A virus (IAV) infection through alterations in surface expression of various markers necessary for migration and cellular immunity responses, according to Le Bonheur research published in the Journal of Leukocyte Biology.
Previous research explored the effects of IAV infection in patients with allergic asthma. During the 2009 influenza pandemic, patients hospitalized with influenza experienced lower morbidity if allergic asthma was an underlying condition. In mice, the researchers reported that the beneficial effect of this co-morbidity correlated with a dramatic increase in eosinophils in the airways, a hallmark of allergic asthma. Eosinophils were susceptible to IAV infection and also presented IAV antigens to CD8+ T-cells, which are heavily involved in resolving viral infections. This implied that eosinophils actively contribute to the antiviral response during influenza. While once considered to be a cell that degranulated after allergen encounters and incidentally promoted host pathology during allergy, this research expanded the role of eosinophils to that of anti-viral mediators and specifically showed that eosinophils are active participants in the resolution of influenza. Many of the processes that cumulate in eosinophils making this valuable contribution are unclear.
“Very little is known about how eosinophils respond to direct exposure to IAV or the microenvironment in which the viral burden is high,” said Le Bonheur Researcher Amali Samarasinghe, PhD. “We hypothesized that eosinophils would dynamically respond to the presence of IAV through phenotypic, transcriptomic and physiologic changes.”
Researchers investigated eosinophil characteristics in different niches in a mouse model of fungal asthma and influenza, as well as responses to in-vitro IAV exposure. Results of the study showed:
Overall, mice with fungal asthma that were protected from severe IAV morbidity had reduced levels of cytokines – which can contribute to pathology when present in excess. When exposed to IAV, eosinophils initiate self-preservation mechanisms to survive viral infection, such as conserving energy by reducing transcription activity and mitochondrial respiration. Concurrently, they increase their ability to recognize IAV and induce epigenetic changes in CD8+ T-cells that initiate their differentiation into cytotoxic cells known to be a critical component of the antiviral response.
“Our research shows that eosinophils respond dynamically to IAV infection and contribute to antiviral host defense mechanisms during influenza,” says Samarasinghe. “This information is important for selecting effective therapeutics for asthmatics that may benefit from eosinophil presence in airways during IAV infection.”
In addition to Samarasinghe, researchers on the project included Kui Li, PhD, Robert Rooney, PhD, and Heather Smallwood, PhD.
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