Maternal gut microbiome regulates immunity to RSV infection in offspring

Development of the immune system can be influenced by diverse extrinsic and intrinsic factors that influence the risk of disease. Severe early life respiratory syncytial virus (RSV) infection is associated with persistent immune alterations. Previously, our group had shown that adult mice orally sup...

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Published inThe Journal of experimental medicine Vol. 218; no. 11
Main Authors Fonseca, Wendy, Malinczak, Carrie-Anne, Fujimura, Kei, Li, Danny, McCauley, Kathryn, Li, Jia, Best, Shannon K K, Zhu, Diana, Rasky, Andrew J, Johnson, Christine C, Bermick, Jennifer, Zoratti, Edward M, Ownby, Dennis, Lynch, Susan V, Lukacs, Nicholas W, Ptaschinski, Catherine
Format Journal Article
LanguageEnglish
Published United States Rockefeller University Press 01.11.2021
Subjects
Animals
Brief Definitive Report
Cytokines - immunology
Disease Models, Animal
Female
Gastrointestinal Microbiome - immunology
Infectious Disease and Host Defense
Lung - immunology
Lung - virology
Mice
Mice, Inbred BALB C
Mucosal Immunology
Pregnancy
Respiratory Syncytial Virus Infections - immunology
Th2 Cells - immunology
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Summary:Development of the immune system can be influenced by diverse extrinsic and intrinsic factors that influence the risk of disease. Severe early life respiratory syncytial virus (RSV) infection is associated with persistent immune alterations. Previously, our group had shown that adult mice orally supplemented with Lactobacillus johnsonii exhibited decreased airway immunopathology following RSV infection. Here, we demonstrate that offspring of mice supplemented with L. johnsonii exhibit reduced airway mucus and Th2 cell-mediated response to RSV infection. Maternal supplementation resulted in a consistent gut microbiome in mothers and their offspring. Importantly, supplemented maternal plasma and breastmilk, and offspring plasma, exhibited decreased inflammatory metabolites. Cross-fostering studies showed that prenatal Lactobacillus exposure led to decreased Th2 cytokines and lung inflammation following RSV infection, while postnatal Lactobacillus exposure diminished goblet cell hypertrophy and mucus production in the lung in response to airway infection. These studies demonstrate that Lactobacillus modulation of the maternal microbiome and associated metabolic reprogramming enhance airway protection against RSV in neonates.
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Disclosures: S.V. Lynch reported personal fees from Siolta Therapeutics Inc. during the conduct of the study and outside the submitted work; in addition, S.V. Lynch had a patent to Reductive prodrug cancer chemothera (Stan449-PRV) issued, a patent to combination antibiotic and antibody therapy for the treatment of Pseudomonas aeruginosa infection (WO 2010091189 A1) issued, a patent to therapeutic microbial consortium for induction of immune tolerance with royalties paid to Siolta Therapeutics Inc., a patent to systems and methods for detecting antibiotic resistance (WO 2012027302 A3) issued, a patent to nitroreductase enzymes (US 7687474 B2) issued, a patent to sinusitis diagnostics and treatments (WO 2013155370 A1) issued, a patent to methods and systems for phylogenetic analysis (US 20120264637 A1) issued, a patent to methods and compositions relating to epoxide hydrolase genes licensed to Siolta Therapeutics Inc., and a patent to novel Lactobacillus and Micrococcus species that promote tolerogenic immunity pending. No other disclosures were reported.
ISSN:0022-1007
1540-9538
DOI:10.1084/jem.20210235