Nanoparticles reduce monocytes within the lungs to improve outcomes after influenza virus infection in aged mice
Older people exhibit dysregulated innate immunity to respiratory viral infections, including influenza and SARS-CoV-2, and show an increase in morbidity and mortality. Nanoparticles are a potential practical therapeutic that could reduce exaggerated innate immune responses within the lungs during vi...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
American Society for Clinical investigation
2022-08-01
|
| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.156320 |
| _version_ | 1797634354855280640 |
|---|---|
| author | William J. Kelley Kathleen M. Wragg Judy Chen Tushar Murthy Qichen Xu Michael T. Boyne Joseph R. Podojil Adam Elhofy Daniel R. Goldstein |
| author_facet | William J. Kelley Kathleen M. Wragg Judy Chen Tushar Murthy Qichen Xu Michael T. Boyne Joseph R. Podojil Adam Elhofy Daniel R. Goldstein |
| author_sort | William J. Kelley |
| collection | DOAJ |
| description | Older people exhibit dysregulated innate immunity to respiratory viral infections, including influenza and SARS-CoV-2, and show an increase in 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 i.v. injection to aged mice at day 3 after infection, when the hyperinflammatory innate immune response was 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, reduced 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 information concerning a practical therapeutic, which, if translated clinically, could improve disease outcomes for vulnerable older patients suffering from respiratory viral infections. |
| first_indexed | 2024-03-11T12:07:28Z |
| format | Article |
| id | doaj.art-4576ad08e65547c38dee32f1176ea356 |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-03-11T12:07:28Z |
| publishDate | 2022-08-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-4576ad08e65547c38dee32f1176ea3562023-11-07T16:24:24ZengAmerican Society for Clinical investigationJCI Insight2379-37082022-08-01715Nanoparticles reduce monocytes within the lungs to improve outcomes after influenza virus infection in aged miceWilliam J. KelleyKathleen M. WraggJudy ChenTushar MurthyQichen XuMichael T. BoyneJoseph R. PodojilAdam ElhofyDaniel R. GoldsteinOlder people exhibit dysregulated innate immunity to respiratory viral infections, including influenza and SARS-CoV-2, and show an increase in 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 i.v. injection to aged mice at day 3 after infection, when the hyperinflammatory innate immune response was 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, reduced 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 information concerning a practical therapeutic, which, if translated clinically, could improve disease outcomes for vulnerable older patients suffering from respiratory viral infections.https://doi.org/10.1172/jci.insight.156320AgingInfectious disease |
| spellingShingle | William J. Kelley Kathleen M. Wragg Judy Chen Tushar Murthy Qichen Xu Michael T. Boyne Joseph R. Podojil Adam Elhofy Daniel R. Goldstein Nanoparticles reduce monocytes within the lungs to improve outcomes after influenza virus infection in aged mice JCI Insight Aging Infectious disease |
| title | Nanoparticles reduce monocytes within the lungs to improve outcomes after influenza virus infection in aged mice |
| title_full | Nanoparticles reduce monocytes within the lungs to improve outcomes after influenza virus infection in aged mice |
| title_fullStr | Nanoparticles reduce monocytes within the lungs to improve outcomes after influenza virus infection in aged mice |
| title_full_unstemmed | Nanoparticles reduce monocytes within the lungs to improve outcomes after influenza virus infection in aged mice |
| title_short | Nanoparticles reduce monocytes within the lungs to improve outcomes after influenza virus infection in aged mice |
| title_sort | nanoparticles reduce monocytes within the lungs to improve outcomes after influenza virus infection in aged mice |
| topic | Aging Infectious disease |
| url | https://doi.org/10.1172/jci.insight.156320 |
| work_keys_str_mv | AT williamjkelley nanoparticlesreducemonocyteswithinthelungstoimproveoutcomesafterinfluenzavirusinfectioninagedmice AT kathleenmwragg nanoparticlesreducemonocyteswithinthelungstoimproveoutcomesafterinfluenzavirusinfectioninagedmice AT judychen nanoparticlesreducemonocyteswithinthelungstoimproveoutcomesafterinfluenzavirusinfectioninagedmice AT tusharmurthy nanoparticlesreducemonocyteswithinthelungstoimproveoutcomesafterinfluenzavirusinfectioninagedmice AT qichenxu nanoparticlesreducemonocyteswithinthelungstoimproveoutcomesafterinfluenzavirusinfectioninagedmice AT michaeltboyne nanoparticlesreducemonocyteswithinthelungstoimproveoutcomesafterinfluenzavirusinfectioninagedmice AT josephrpodojil nanoparticlesreducemonocyteswithinthelungstoimproveoutcomesafterinfluenzavirusinfectioninagedmice AT adamelhofy nanoparticlesreducemonocyteswithinthelungstoimproveoutcomesafterinfluenzavirusinfectioninagedmice AT danielrgoldstein nanoparticlesreducemonocyteswithinthelungstoimproveoutcomesafterinfluenzavirusinfectioninagedmice |