Nanoparticles reduce monocytes within the lungs to improve outcomes after influenza virus infection in aged mice

William J. Kelley; Kathleen M. Wragg; Judy Chen; Tushar Murthy; Qichen Xu; Michael T. Boyne II; Joseph R. Podojil; Adam Elhofy; Daniel R. Goldstein

doi:10.1172/jci.insight.156320

Nanoparticles reduce monocytes within the lungs to improve outcomes after influenza virus infection in aged mice

William J. Kelley,¹ Kathleen M. Wragg,¹ Judy Chen,¹ Tushar Murthy,² Qichen Xu,² Michael T. Boyne II,² Joseph R. Podojil,² Adam Elhofy,² and Daniel R. Goldstein³

Published June 23, 2022 - More info

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Abstract

Older people exhibit dysregulated innate immunity to respiratory viral infections, including influenza and SARS-CoV-2, to increase morbidity and mortality. Nanoparticles are a potential practical therapeutic that could reduce exaggerated innate immune responses within the lungs during viral infection. However, such therapeutics have not been examined for effectiveness during respiratory viral infection, particular in aged hosts. Here, we employed a lethal model of influenza viral infection in vulnerable aged mice to examine the ability of biodegradable, cargo-free nanoparticles, designated ONP-302, to resolve innate immune dysfunction and improve outcomes during infection. We administered ONP-302 via intravenous injection to aged mice at day 3 post-infection when the hyperinflammatory innate immune response is already established. During infection, we found that ONP-302 treatment reduced the numbers of inflammatory monocytes within the lungs and increased their number in both the liver and spleen, without impacting viral clearance. Importantly, cargo-free nanoparticles reduced lung damage, histological lung inflammation and improved gas exchange and, ultimately, the clinical outcomes in influenza-infected aged mice. In conclusion, ONP-302 improves outcomes in influenza-infected aged mice. Thus, our study provides fundamental information concerning a practical therapeutic which, if translated clinically, could improve disease outcomes for vulnerable older patients suffering from respiratory viral infections.

Nanoparticles reduce monocytes within the lungs to improve outcomes after influenza virus infection in aged mice

William J. Kelley,¹ Kathleen M. Wragg,¹ Judy Chen,¹ Tushar Murthy,² Qichen Xu,² Michael T. Boyne II,² Joseph R. Podojil,² Adam Elhofy,² and Daniel R. Goldstein³

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Nanoparticles reduce monocytes within the lungs to improve outcomes after influenza virus infection in aged mice

William J. Kelley,1 Kathleen M. Wragg,1 Judy Chen,1 Tushar Murthy,2 Qichen Xu,2 Michael T. Boyne II,2 Joseph R. Podojil,2 Adam Elhofy,2 and Daniel R. Goldstein3

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William J. Kelley,¹ Kathleen M. Wragg,¹ Judy Chen,¹ Tushar Murthy,² Qichen Xu,² Michael T. Boyne II,² Joseph R. Podojil,² Adam Elhofy,² and Daniel R. Goldstein³