Protection against neonatal respiratory viral infection via maternal treatment during pregnancy with the benign immune training agent OM-85
| Autor: | Deborah H. Strickland, Philip A. Stumbles, Jean Francois Lauzon-Joset, Patrick G. Holt, Kyle T Mincham, Yasmine Khandan, Naomi M. Scott |
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| Rok vydání: | 2021 |
| Předmět: |
Offspring
Immunology early‐life infection severity medicine.disease_cause lung Immune system medicine Immunology and Allergy Respiratory system General Nursing Pregnancy Lung Innate immune system immune modulation business.industry OM‐85 RC581-607 medicine.disease medicine.anatomical_structure rhinovirus TLR4 Original Article pregnancy Immunologic diseases. Allergy Rhinovirus business |
| Zdroj: | Clinical & Translational Immunology Clinical & Translational Immunology, Vol 10, Iss 7, Pp n/a-n/a (2021) |
| ISSN: | 2050-0068 |
| Popis: | 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. Infancy represents the period of maximal risk for both severe respiratory infections and blunted responsiveness to vaccines. Here, we provide proof of concept for a novel solution to this problem through maternal oral treatment during pregnancy with the benign microbe‐derived immune‐modulating agent OM‐85, already in widespread human clinical use in infants. |
| Databáze: | OpenAIRE |
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