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Protection against neonatal respiratory viral infection via maternal treatment during pregnancy with the benign immune training agent OM‐85

OBJECTIVES: Incomplete maturation of immune regulatory functions at birth is antecedent to the heightened risk for severe respiratory infections during infancy. Our forerunner animal model studies demonstrated that maternal treatment with the microbial‐derived immune training agent OM‐85 during preg...

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Autores principales: Lauzon‐Joset, Jean‐Francois, Mincham, Kyle T, Scott, Naomi M, Khandan, Yasmine, Stumbles, Philip A, Holt, Patrick G, Strickland, Deborah H
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248556/
https://www.ncbi.nlm.nih.gov/pubmed/34249358
http://dx.doi.org/10.1002/cti2.1303
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author Lauzon‐Joset, Jean‐Francois
Mincham, Kyle T
Scott, Naomi M
Khandan, Yasmine
Stumbles, Philip A
Holt, Patrick G
Strickland, Deborah H
author_facet Lauzon‐Joset, Jean‐Francois
Mincham, Kyle T
Scott, Naomi M
Khandan, Yasmine
Stumbles, Philip A
Holt, Patrick G
Strickland, Deborah H
author_sort Lauzon‐Joset, Jean‐Francois
collection PubMed
description OBJECTIVES: Incomplete maturation of immune regulatory functions at birth is antecedent to the heightened risk for severe respiratory infections during infancy. Our forerunner animal model studies demonstrated that maternal treatment with the microbial‐derived immune training agent OM‐85 during pregnancy promotes accelerated postnatal maturation of mechanisms that regulate inflammatory processes in the offspring airways. Here, we aimed to provide proof of concept for a novel solution to reduce the burden and potential long‐term sequelae of severe early‐life respiratory viral infection through maternal oral treatment during pregnancy with OM‐85, already in widespread human clinical use. METHODS: In this study, we performed flow cytometry and targeted gene expression (RT‐qPCR) analysis on lungs from neonatal offspring whose mothers received oral OM‐85 treatment during pregnancy. We next determined whether neonatal offspring from OM‐85 treated mothers demonstrate enhanced protection against lethal lower respiratory infection with mouse‐adapted rhinovirus (vMC(0)), and associated lung immune changes. RESULTS: Offspring from mothers treated with OM‐85 during pregnancy display accelerated postnatal seeding of lung myeloid populations demonstrating upregulation of function‐associated markers. Offspring from OM‐85 mothers additionally exhibit enhanced expression of TLR4/7 and the IL‐1β/NLRP3 inflammasome complex within the lung. These treatment effects were associated with enhanced capacity to clear an otherwise lethal respiratory viral infection during the neonatal period, with concomitant regulation of viral‐induced IFN response intensity. CONCLUSION: These results demonstrate that maternal OM‐85 treatment protects offspring against lethal neonatal respiratory viral infection by accelerating development of innate immune mechanisms crucial for maintenance of local immune homeostasis in the face of pathogen challenge.
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spelling pubmed-82485562021-07-09 Protection against neonatal respiratory viral infection via maternal treatment during pregnancy with the benign immune training agent OM‐85 Lauzon‐Joset, Jean‐Francois Mincham, Kyle T Scott, Naomi M Khandan, Yasmine Stumbles, Philip A Holt, Patrick G Strickland, Deborah H Clin Transl Immunology Original Article OBJECTIVES: Incomplete maturation of immune regulatory functions at birth is antecedent to the heightened risk for severe respiratory infections during infancy. Our forerunner animal model studies demonstrated that maternal treatment with the microbial‐derived immune training agent OM‐85 during pregnancy promotes accelerated postnatal maturation of mechanisms that regulate inflammatory processes in the offspring airways. Here, we aimed to provide proof of concept for a novel solution to reduce the burden and potential long‐term sequelae of severe early‐life respiratory viral infection through maternal oral treatment during pregnancy with OM‐85, already in widespread human clinical use. METHODS: In this study, we performed flow cytometry and targeted gene expression (RT‐qPCR) analysis on lungs from neonatal offspring whose mothers received oral OM‐85 treatment during pregnancy. We next determined whether neonatal offspring from OM‐85 treated mothers demonstrate enhanced protection against lethal lower respiratory infection with mouse‐adapted rhinovirus (vMC(0)), and associated lung immune changes. RESULTS: Offspring from mothers treated with OM‐85 during pregnancy display accelerated postnatal seeding of lung myeloid populations demonstrating upregulation of function‐associated markers. Offspring from OM‐85 mothers additionally exhibit enhanced expression of TLR4/7 and the IL‐1β/NLRP3 inflammasome complex within the lung. These treatment effects were associated with enhanced capacity to clear an otherwise lethal respiratory viral infection during the neonatal period, with concomitant regulation of viral‐induced IFN response intensity. CONCLUSION: These results demonstrate that maternal OM‐85 treatment protects offspring against lethal neonatal respiratory viral infection by accelerating development of innate immune mechanisms crucial for maintenance of local immune homeostasis in the face of pathogen challenge. John Wiley and Sons Inc. 2021-07-01 /pmc/articles/PMC8248556/ /pubmed/34249358 http://dx.doi.org/10.1002/cti2.1303 Text en © 2021 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Article
Lauzon‐Joset, Jean‐Francois
Mincham, Kyle T
Scott, Naomi M
Khandan, Yasmine
Stumbles, Philip A
Holt, Patrick G
Strickland, Deborah H
Protection against neonatal respiratory viral infection via maternal treatment during pregnancy with the benign immune training agent OM‐85
title Protection against neonatal respiratory viral infection via maternal treatment during pregnancy with the benign immune training agent OM‐85
title_full Protection against neonatal respiratory viral infection via maternal treatment during pregnancy with the benign immune training agent OM‐85
title_fullStr Protection against neonatal respiratory viral infection via maternal treatment during pregnancy with the benign immune training agent OM‐85
title_full_unstemmed Protection against neonatal respiratory viral infection via maternal treatment during pregnancy with the benign immune training agent OM‐85
title_short Protection against neonatal respiratory viral infection via maternal treatment during pregnancy with the benign immune training agent OM‐85
title_sort protection against neonatal respiratory viral infection via maternal treatment during pregnancy with the benign immune training agent om‐85
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248556/
https://www.ncbi.nlm.nih.gov/pubmed/34249358
http://dx.doi.org/10.1002/cti2.1303
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