Influenza A Virus and Eosinophils: A Charged Interaction

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.

“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:

1. Mice with fungal allergic asthma have a lower proinflammatory cytokine profile in their lungs during influenza than non-allergic mice.
2. Eosinophil surface antigens are differentially regulated in mice with fungal asthma and influenza. During influenza, eosinophils changed the surface expression of proteins involved in antigen presentation, activation and survival depending on both niche and allergic environment.
3. Following virus exposure, a discrete subset of eosinophils that decreased their surface expression of Siglec-F were also more active. Siglec-Flo expressors also increased expression of eosinophil survival receptor IL-5R and downregulated CD62L which is associated with activation. These data suggest that subpopulations of eosinophils may have differing functions during IAV infection.
4. IAV exposure alters the eosinophil transcriptome. IAV infected eosinophils reduced overall transcriptional activity but upregulated transcription of mRNAs encoding viral recognition proteins.
5. Eosinophils reduce mitochondrial respiration in response to IAV. Eosinophils had a lowered basal respiration rate and an overall reduction in mitochondrial respiration.
6. Flu-PB-1 pulsed eosinophils promote the generation of cytotoxic CD8+ T-cells by causing demethylation of the Tbx21 locus. IAV-exposed eosinophils can communicate with CD8+ T-cells, resulting in epigenetic changes that allow the differentiation of IAV-specific CD8+ T-cells into effector cells.

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.

LeMessurier KS, Rooney R, Ghoneim HE, et al. Influenza A virus directly modulates mouse eosinophil responses [published online ahead of print, 2020 May 9]. J Leukoc Biol. 2020; 10.1002/ JLB.4MA0320-343R. doi:10.1002/JLB.4MA0320-343R