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ResearchIn-Press PreviewAgingInfectious disease Open Access | 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

1Department of Internal Medicine, University of Michigan, Ann Arbor, United States of America

2Research and Development, COUR Pharmaceutical, Northbrook, United States of America

3Michigan Biology of Cardiovascular Aging, University of Michigan, Ann Arbor, United States of America

Find articles by Kelley, W. in: JCI | PubMed | Google Scholar

1Department of Internal Medicine, University of Michigan, Ann Arbor, United States of America

2Research and Development, COUR Pharmaceutical, Northbrook, United States of America

3Michigan Biology of Cardiovascular Aging, University of Michigan, Ann Arbor, United States of America

Find articles by Wragg, K. in: JCI | PubMed | Google Scholar

1Department of Internal Medicine, University of Michigan, Ann Arbor, United States of America

2Research and Development, COUR Pharmaceutical, Northbrook, United States of America

3Michigan Biology of Cardiovascular Aging, University of Michigan, Ann Arbor, United States of America

Find articles by Chen, J. in: JCI | PubMed | Google Scholar |

1Department of Internal Medicine, University of Michigan, Ann Arbor, United States of America

2Research and Development, COUR Pharmaceutical, Northbrook, United States of America

3Michigan Biology of Cardiovascular Aging, University of Michigan, Ann Arbor, United States of America

Find articles by Murthy, T. in: JCI | PubMed | Google Scholar

1Department of Internal Medicine, University of Michigan, Ann Arbor, United States of America

2Research and Development, COUR Pharmaceutical, Northbrook, United States of America

3Michigan Biology of Cardiovascular Aging, University of Michigan, Ann Arbor, United States of America

Find articles by Xu, Q. in: JCI | PubMed | Google Scholar

1Department of Internal Medicine, University of Michigan, Ann Arbor, United States of America

2Research and Development, COUR Pharmaceutical, Northbrook, United States of America

3Michigan Biology of Cardiovascular Aging, University of Michigan, Ann Arbor, United States of America

Find articles by Boyne II, M. in: JCI | PubMed | Google Scholar

1Department of Internal Medicine, University of Michigan, Ann Arbor, United States of America

2Research and Development, COUR Pharmaceutical, Northbrook, United States of America

3Michigan Biology of Cardiovascular Aging, University of Michigan, Ann Arbor, United States of America

Find articles by Podojil, J. in: JCI | PubMed | Google Scholar |

1Department of Internal Medicine, University of Michigan, Ann Arbor, United States of America

2Research and Development, COUR Pharmaceutical, Northbrook, United States of America

3Michigan Biology of Cardiovascular Aging, University of Michigan, Ann Arbor, United States of America

Find articles by Elhofy, A. in: JCI | PubMed | Google Scholar

1Department of Internal Medicine, University of Michigan, Ann Arbor, United States of America

2Research and Development, COUR Pharmaceutical, Northbrook, United States of America

3Michigan Biology of Cardiovascular Aging, University of Michigan, Ann Arbor, United States of America

Find articles by Goldstein, D. in: JCI | PubMed | Google Scholar |

Published June 23, 2022 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.156320.
Copyright © 2022, Kelley et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published June 23, 2022 - Version history
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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.

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