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Lung transcriptional unresponsiveness and loss of early influenza virus control in infected neonates is prevented by intranasal Lactobacillus rhamnosus GG

Respiratory viral infections contribute substantially to global infant losses and disproportionately affect preterm neonates. Using our previously established neonatal murine model of influenza infection, we demonstrate that three-day old mice are exceptionally sensitive to influenza virus infection...

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Autores principales: Kumova, Ogan K., Fike, Adam J., Thayer, Jillian L., Nguyen, Linda T., Mell, Joshua Chang, Pascasio, Judy, Stairiker, Christopher, Leon, Leticia G., Katsikis, Peter D., Carey, Alison J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6808501/
https://www.ncbi.nlm.nih.gov/pubmed/31603951
http://dx.doi.org/10.1371/journal.ppat.1008072
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author Kumova, Ogan K.
Fike, Adam J.
Thayer, Jillian L.
Nguyen, Linda T.
Mell, Joshua Chang
Pascasio, Judy
Stairiker, Christopher
Leon, Leticia G.
Katsikis, Peter D.
Carey, Alison J.
author_facet Kumova, Ogan K.
Fike, Adam J.
Thayer, Jillian L.
Nguyen, Linda T.
Mell, Joshua Chang
Pascasio, Judy
Stairiker, Christopher
Leon, Leticia G.
Katsikis, Peter D.
Carey, Alison J.
author_sort Kumova, Ogan K.
collection PubMed
description Respiratory viral infections contribute substantially to global infant losses and disproportionately affect preterm neonates. Using our previously established neonatal murine model of influenza infection, we demonstrate that three-day old mice are exceptionally sensitive to influenza virus infection and exhibit high mortality and viral load. Intranasal pre- and post-treatment of neonatal mice with Lactobacillus rhamnosus GG (LGG), an immune modulator in respiratory viral infection of adult mice and human preterm neonates, considerably improves neonatal mice survival after influenza virus infection. We determine that both live and heat-killed intranasal LGG are equally efficacious in protection of neonates. Early in influenza infection, neonatal transcriptional responses in the lung are delayed compared to adults. These responses increase by 24 hours post-infection, demonstrating a delay in the kinetics of the neonatal anti-viral response. LGG pretreatment improves immune gene transcriptional responses during early infection and specifically upregulates type I IFN pathways. This is critical for protection, as neonatal mice intranasally pre-treated with IFNβ before influenza virus infection are also protected. Using transgenic mice, we demonstrate that the protective effect of LGG is mediated through a MyD88-dependent mechanism, specifically via TLR4. LGG can improve both early control of virus and transcriptional responsiveness and could serve as a simple and safe intervention to protect neonates.
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spelling pubmed-68085012019-11-02 Lung transcriptional unresponsiveness and loss of early influenza virus control in infected neonates is prevented by intranasal Lactobacillus rhamnosus GG Kumova, Ogan K. Fike, Adam J. Thayer, Jillian L. Nguyen, Linda T. Mell, Joshua Chang Pascasio, Judy Stairiker, Christopher Leon, Leticia G. Katsikis, Peter D. Carey, Alison J. PLoS Pathog Research Article Respiratory viral infections contribute substantially to global infant losses and disproportionately affect preterm neonates. Using our previously established neonatal murine model of influenza infection, we demonstrate that three-day old mice are exceptionally sensitive to influenza virus infection and exhibit high mortality and viral load. Intranasal pre- and post-treatment of neonatal mice with Lactobacillus rhamnosus GG (LGG), an immune modulator in respiratory viral infection of adult mice and human preterm neonates, considerably improves neonatal mice survival after influenza virus infection. We determine that both live and heat-killed intranasal LGG are equally efficacious in protection of neonates. Early in influenza infection, neonatal transcriptional responses in the lung are delayed compared to adults. These responses increase by 24 hours post-infection, demonstrating a delay in the kinetics of the neonatal anti-viral response. LGG pretreatment improves immune gene transcriptional responses during early infection and specifically upregulates type I IFN pathways. This is critical for protection, as neonatal mice intranasally pre-treated with IFNβ before influenza virus infection are also protected. Using transgenic mice, we demonstrate that the protective effect of LGG is mediated through a MyD88-dependent mechanism, specifically via TLR4. LGG can improve both early control of virus and transcriptional responsiveness and could serve as a simple and safe intervention to protect neonates. Public Library of Science 2019-10-11 /pmc/articles/PMC6808501/ /pubmed/31603951 http://dx.doi.org/10.1371/journal.ppat.1008072 Text en © 2019 Kumova et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Kumova, Ogan K.
Fike, Adam J.
Thayer, Jillian L.
Nguyen, Linda T.
Mell, Joshua Chang
Pascasio, Judy
Stairiker, Christopher
Leon, Leticia G.
Katsikis, Peter D.
Carey, Alison J.
Lung transcriptional unresponsiveness and loss of early influenza virus control in infected neonates is prevented by intranasal Lactobacillus rhamnosus GG
title Lung transcriptional unresponsiveness and loss of early influenza virus control in infected neonates is prevented by intranasal Lactobacillus rhamnosus GG
title_full Lung transcriptional unresponsiveness and loss of early influenza virus control in infected neonates is prevented by intranasal Lactobacillus rhamnosus GG
title_fullStr Lung transcriptional unresponsiveness and loss of early influenza virus control in infected neonates is prevented by intranasal Lactobacillus rhamnosus GG
title_full_unstemmed Lung transcriptional unresponsiveness and loss of early influenza virus control in infected neonates is prevented by intranasal Lactobacillus rhamnosus GG
title_short Lung transcriptional unresponsiveness and loss of early influenza virus control in infected neonates is prevented by intranasal Lactobacillus rhamnosus GG
title_sort lung transcriptional unresponsiveness and loss of early influenza virus control in infected neonates is prevented by intranasal lactobacillus rhamnosus gg
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6808501/
https://www.ncbi.nlm.nih.gov/pubmed/31603951
http://dx.doi.org/10.1371/journal.ppat.1008072
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