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Excessive neutrophil levels in the lung underlie the age-associated increase in influenza mortality

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  • Excessive neutrophil levels in the lung underlie the age-associated increase in influenza mortality

    Mucosal Immunol. 2019 Jan 7. doi: 10.1038/s41385-018-0115-3. [Epub ahead of print]
    Excessive neutrophil levels in the lung underlie the age-associated increase in influenza mortality.

    Kulkarni U1, Zemans RL1, Smith CA1, Wood SC1, Deng JC1, Goldstein DR2,3,4.
    Author information

    Abstract

    Neutrophils clear viruses, but excessive neutrophil responses induce tissue injury and worsen disease. Aging increases mortality to influenza infection; however, whether this is due to impaired viral clearance or a pathological host immune response is unknown. Here we show that aged mice have higher levels of lung neutrophils than younger mice after influenza viral infection. Depleting neutrophils after, but not before, infection substantially improves the survival of aged mice without altering viral clearance. Aged alveolar epithelial cells (AECs) have a higher frequency of senescence and secrete higher levels of the neutrophil-attracting chemokines CXCL1 and CXCL2 during influenza infection. These chemokines are required for age-enhanced neutrophil chemotaxis in vitro. Our work suggests that aging increases mortality from influenza in part because senescent AECs secrete more chemokines, leading to excessive neutrophil recruitment. Therapies that mitigate this pathological immune response in the elderly might improve outcomes of influenza and other respiratory infections.


    PMID: 30617300 DOI: 10.1038/s41385-018-0115-3
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