Protection against neonatal respiratory viral infection via maternal treatment during pregnancy with the benign immune training agent OM‐85
Abstract 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 dur...
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Online Access: | https://doi.org/10.1002/cti2.1303 |
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doaj-fa8d03d0ce44418eb1c52a7fbc1a765a2021-07-27T06:50:31ZengWileyClinical & Translational Immunology2050-00682021-01-01107n/an/a10.1002/cti2.1303Protection against neonatal respiratory viral infection via maternal treatment during pregnancy with the benign immune training agent OM‐85Jean‐Francois Lauzon‐Joset0Kyle T Mincham1Naomi M Scott2Yasmine Khandan3Philip A Stumbles4Patrick G Holt5Deborah H Strickland6Centre de Recherche Institut Universitaire de Cardiologie et de Pneumologie de Québec Université Laval Québec QC CanadaTelethon Kids Institute University of Western Australia Nedlands WA AustraliaTelethon Kids Institute University of Western Australia Nedlands WA AustraliaTelethon Kids Institute University of Western Australia Nedlands WA AustraliaTelethon Kids Institute University of Western Australia Nedlands WA AustraliaTelethon Kids Institute University of Western Australia Nedlands WA AustraliaTelethon Kids Institute University of Western Australia Nedlands WA AustraliaAbstract 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 (vMC0), 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.https://doi.org/10.1002/cti2.1303early‐life infection severityimmune modulationlungOM‐85pregnancyrhinovirus |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jean‐Francois Lauzon‐Joset Kyle T Mincham Naomi M Scott Yasmine Khandan Philip A Stumbles Patrick G Holt Deborah H Strickland |
spellingShingle |
Jean‐Francois Lauzon‐Joset Kyle T Mincham Naomi M Scott Yasmine Khandan Philip A Stumbles Patrick G Holt Deborah H Strickland Protection against neonatal respiratory viral infection via maternal treatment during pregnancy with the benign immune training agent OM‐85 Clinical & Translational Immunology early‐life infection severity immune modulation lung OM‐85 pregnancy rhinovirus |
author_facet |
Jean‐Francois Lauzon‐Joset Kyle T Mincham Naomi M Scott Yasmine Khandan Philip A Stumbles Patrick G Holt Deborah H Strickland |
author_sort |
Jean‐Francois Lauzon‐Joset |
title |
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_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_sort |
protection against neonatal respiratory viral infection via maternal treatment during pregnancy with the benign immune training agent om‐85 |
publisher |
Wiley |
series |
Clinical & Translational Immunology |
issn |
2050-0068 |
publishDate |
2021-01-01 |
description |
Abstract 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 (vMC0), 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. |
topic |
early‐life infection severity immune modulation lung OM‐85 pregnancy rhinovirus |
url |
https://doi.org/10.1002/cti2.1303 |
work_keys_str_mv |
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