Cargando…

Severity of neonatal influenza infection is driven by type I interferon and oxidative stress

Neonates exhibit increased susceptibility to respiratory viral infections, attributed to inflammation at the developing pulmonary air-blood interface. IFN I are anti-viral cytokines critical to control viral replication, but also promote inflammation. Previously, we established a neonatal murine inf...

Descripción completa

Detalles Bibliográficos
Autores principales: Kumova, Ogan K., Galani, Ioanna-Evdokia, Rao, Abhishek, Johnson, Hannah, Triantafyllia, Vasiliki, Matt, Stephanie M., Pascasio, Judy, Gaskill, Peter J., Andreakos, Evangelos, Katsikis, Peter D., Carey, Alison J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9724789/
https://www.ncbi.nlm.nih.gov/pubmed/36352099
http://dx.doi.org/10.1038/s41385-022-00576-x
_version_ 1784844490937204736
author Kumova, Ogan K.
Galani, Ioanna-Evdokia
Rao, Abhishek
Johnson, Hannah
Triantafyllia, Vasiliki
Matt, Stephanie M.
Pascasio, Judy
Gaskill, Peter J.
Andreakos, Evangelos
Katsikis, Peter D.
Carey, Alison J.
author_facet Kumova, Ogan K.
Galani, Ioanna-Evdokia
Rao, Abhishek
Johnson, Hannah
Triantafyllia, Vasiliki
Matt, Stephanie M.
Pascasio, Judy
Gaskill, Peter J.
Andreakos, Evangelos
Katsikis, Peter D.
Carey, Alison J.
author_sort Kumova, Ogan K.
collection PubMed
description Neonates exhibit increased susceptibility to respiratory viral infections, attributed to inflammation at the developing pulmonary air-blood interface. IFN I are anti-viral cytokines critical to control viral replication, but also promote inflammation. Previously, we established a neonatal murine influenza model, which demonstrates increased mortality. Here, we sought to determine the role of IFN I in this increased mortality. We found that three-day-old IFNAR-deficient mice are highly protected from IV-induced mortality. In addition, exposure to IFNβ 24-hours post-IV infection accelerated death in WT neonatal animals but did not impact adult mortality. In contrast, IFN IIIs are protective to neonatal mice. IFNβ induced an oxidative stress imbalance specifically in primary neonatal IV-infected pulmonary type II epithelial cells (TIIEC), not in adult TIIECs. Moreover, neonates did not have an infection-induced increase in antioxidants, including a key antioxidant, superoxide dismutase 3, as compared to adults. Importantly, antioxidant treatment rescued IV-infected neonatal mice, but had no impact on adult morbidity. We propose that IFN I exacerbate an oxidative stress imbalance in the neonate because of IFN I-induced pulmonary TIIEC ROS production coupled with developmentally regulated, defective antioxidant production in response to IV infection. This age-specific imbalance contributes to mortality after respiratory infections in this vulnerable population.
format Online
Article
Text
id pubmed-9724789
institution National Center for Biotechnology Information
language English
publishDate 2022
record_format MEDLINE/PubMed
spelling pubmed-97247892023-05-09 Severity of neonatal influenza infection is driven by type I interferon and oxidative stress Kumova, Ogan K. Galani, Ioanna-Evdokia Rao, Abhishek Johnson, Hannah Triantafyllia, Vasiliki Matt, Stephanie M. Pascasio, Judy Gaskill, Peter J. Andreakos, Evangelos Katsikis, Peter D. Carey, Alison J. Mucosal Immunol Article Neonates exhibit increased susceptibility to respiratory viral infections, attributed to inflammation at the developing pulmonary air-blood interface. IFN I are anti-viral cytokines critical to control viral replication, but also promote inflammation. Previously, we established a neonatal murine influenza model, which demonstrates increased mortality. Here, we sought to determine the role of IFN I in this increased mortality. We found that three-day-old IFNAR-deficient mice are highly protected from IV-induced mortality. In addition, exposure to IFNβ 24-hours post-IV infection accelerated death in WT neonatal animals but did not impact adult mortality. In contrast, IFN IIIs are protective to neonatal mice. IFNβ induced an oxidative stress imbalance specifically in primary neonatal IV-infected pulmonary type II epithelial cells (TIIEC), not in adult TIIECs. Moreover, neonates did not have an infection-induced increase in antioxidants, including a key antioxidant, superoxide dismutase 3, as compared to adults. Importantly, antioxidant treatment rescued IV-infected neonatal mice, but had no impact on adult morbidity. We propose that IFN I exacerbate an oxidative stress imbalance in the neonate because of IFN I-induced pulmonary TIIEC ROS production coupled with developmentally regulated, defective antioxidant production in response to IV infection. This age-specific imbalance contributes to mortality after respiratory infections in this vulnerable population. 2022-06 2022-11-09 /pmc/articles/PMC9724789/ /pubmed/36352099 http://dx.doi.org/10.1038/s41385-022-00576-x Text en http://www.nature.com/authors/editorial_policies/license.html#termsUsers may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Kumova, Ogan K.
Galani, Ioanna-Evdokia
Rao, Abhishek
Johnson, Hannah
Triantafyllia, Vasiliki
Matt, Stephanie M.
Pascasio, Judy
Gaskill, Peter J.
Andreakos, Evangelos
Katsikis, Peter D.
Carey, Alison J.
Severity of neonatal influenza infection is driven by type I interferon and oxidative stress
title Severity of neonatal influenza infection is driven by type I interferon and oxidative stress
title_full Severity of neonatal influenza infection is driven by type I interferon and oxidative stress
title_fullStr Severity of neonatal influenza infection is driven by type I interferon and oxidative stress
title_full_unstemmed Severity of neonatal influenza infection is driven by type I interferon and oxidative stress
title_short Severity of neonatal influenza infection is driven by type I interferon and oxidative stress
title_sort severity of neonatal influenza infection is driven by type i interferon and oxidative stress
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9724789/
https://www.ncbi.nlm.nih.gov/pubmed/36352099
http://dx.doi.org/10.1038/s41385-022-00576-x
work_keys_str_mv AT kumovaogank severityofneonatalinfluenzainfectionisdrivenbytypeiinterferonandoxidativestress
AT galaniioannaevdokia severityofneonatalinfluenzainfectionisdrivenbytypeiinterferonandoxidativestress
AT raoabhishek severityofneonatalinfluenzainfectionisdrivenbytypeiinterferonandoxidativestress
AT johnsonhannah severityofneonatalinfluenzainfectionisdrivenbytypeiinterferonandoxidativestress
AT triantafylliavasiliki severityofneonatalinfluenzainfectionisdrivenbytypeiinterferonandoxidativestress
AT mattstephaniem severityofneonatalinfluenzainfectionisdrivenbytypeiinterferonandoxidativestress
AT pascasiojudy severityofneonatalinfluenzainfectionisdrivenbytypeiinterferonandoxidativestress
AT gaskillpeterj severityofneonatalinfluenzainfectionisdrivenbytypeiinterferonandoxidativestress
AT andreakosevangelos severityofneonatalinfluenzainfectionisdrivenbytypeiinterferonandoxidativestress
AT katsikispeterd severityofneonatalinfluenzainfectionisdrivenbytypeiinterferonandoxidativestress
AT careyalisonj severityofneonatalinfluenzainfectionisdrivenbytypeiinterferonandoxidativestress