Influenza A virus directly modulates eosinophil responses

August 05, 2020

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 research published in the Journal of Leukocyte Biology by researchers from Le Bonheur Children's Hospital and the University of Tennessee Health Science Center.

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, which is 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 contributed to expand 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 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 and UTHSC 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 mice using a mouse model of fungal asthma and influenza, in addition to responses when exposed to IAV in vitro.

Results of the study included the following: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" said Samarasinghe. "This information is important for selecting effective therapeutics for asthmatics that may benefit from eosinophil presence in airways during IAV infection."
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About Le Bonheur Children's:

Le Bonheur Children's Hospital in Memphis, Tenn., treats children through community programs, regional clinics and a 255-bed state-of-the-art hospital. Le Bonheur serves as a primary teaching affiliate for the University Tennessee Health Science Center and trains more than 350 pediatricians and specialists each year. Nationally recognized, Le Bonheur is ranked by U.S. News & World Report as a Best Children's Hospital.

For more information, please call (901) 287-6030 or visit lebonheur.org. Connect with us at facebook.com/lebonheurchildrens, twitter.com/lebonheurchild or on Instagram at lebonheurchildrens.

About University of Tennessee Health Science Center:

As Tennessee's only public, statewide, academic health system, the mission of the University of Tennessee Health Science Center is to bring the benefits of the health sciences to the achievement and maintenance of human health through education, research, clinical care, and public service, with a focus on the citizens of Tennessee and the region. The main campus in Memphis includes six colleges: Dentistry, Graduate Health Sciences, Health Professions, Medicine, Nursing and Pharmacy. UTHSC also educates and trains medicine, pharmacy, and/or health professions students, as well as medical residents and fellows, at major sites in Knoxville, Chattanooga and Nashville. For more information, visit http://www.uthsc.edu. Find us on Facebook: facebook.com/uthsc, on Twitter: twitter.com/uthsc and on Instagram: instagram.com/uthsc.

Le Bonheur Children's Hospital

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