Eosinophils are multifunctional cells of the innate immune system linked to allergic inflammation. Asthmatics were more likely to be hospitalized but less likely to suffer severe morbidity and mortality during the 2009 influenza pandemic. These epidemiologic findings were recapitulated in a mouse model of fungal asthma wherein infection during heightened allergic inflammation was protective against influenza A virus (IAV) infection and disease. Our goal was to delineate a mechanism(s) by which allergic asthma may alleviate influenza disease outcome, focused on the hypothesis that pulmonary eosinophilia linked with allergic respiratory disease is able to promote antiviral host defenses against the influenza virus. The transfer of eosinophils from the lungs of allergen-sensitized and challenged mice into influenza virus–infected mice resulted in reduced morbidity and viral burden, improved lung compliance, and increased CD8+ T cell numbers in the airways. In vitro assays with primary or bone marrow–derived eosinophils were used to determine eosinophil responses to the virus using the laboratory strain (A/PR/08/1934) or the pandemic strain (A/CA/04/2009) of IAV. Eosinophils were susceptible to IAV infection and responded by activation, piecemeal degranulation, and upregulation of Ag presentation markers. Virus- or viral peptide–exposed eosinophils induced CD8+ T cell proliferation, activation, and effector functions. Our data suggest that eosinophils promote host cellular immunity to reduce influenza virus replication in lungs, thereby providing a novel mechanism by which hosts with allergic asthma may be protected from influenza morbidity.
This work was supported by the National Institute of Allergy and Infectious Diseases, Contract HHSN2662007000005C, Centers of Excellence in Influenza Research and Surveillance Grant N 01 7005C (J.A.M.), a Le Bonheur Children’s Foundation Junior Faculty Grant, a Bea Gerber Award, and a Young Investigator Award (A.E.S.), an American Lung Association Biomedical Research Grant (A.E.S.), National Heart, Lung, and Blood Institute Grant HL065228 (J.J.L.), Conselho Nacional de Desenvolvimento Científico e Tecnológico (Brazil), and Fundação de Amparo à Pesquisa do Estado de Minas Gerais (Brazil) (R.C.N.M.).
The online version of this article contains supplemental material.
- Received May 5, 2016.
- Accepted February 11, 2017.
- Copyright © 2017 by The American Association of Immunologists, Inc.
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