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Induction of Trained Immunity Protects Neonatal Mice Against Microbial Sepsis by Boosting Both the Inflammatory Response and Antimicrobial Activity.

dc.contributor.authorZhou, Huiting
dc.contributor.authorLu, Xiaying
dc.contributor.authorHuang, Jie
dc.contributor.authorJordan, Patrick
dc.contributor.authorMa, Shurong
dc.contributor.authorXu, Lingqi
dc.contributor.authorHu, Fangjie
dc.contributor.authorGui, Huan
dc.contributor.authorZhao, He
dc.contributor.authorBai, Zhenjiang
dc.contributor.authorRedmond, H Paul
dc.contributor.authorWang, Jiang Huai
dc.contributor.authorWang, Jian
dc.date.accessioned2024-07-19T09:03:52Z
dc.date.available2024-07-19T09:03:52Z
dc.date.issued2022-07-07
dc.identifier.issn1178-7031
dc.identifier.pmid35836719
dc.identifier.doi10.2147/JIR.S363995
dc.identifier.urihttp://hdl.handle.net/10147/642326
dc.descriptionBackground Neonates are susceptible to a wide range of microbial infection and at a high risk to develop severe sepsis and septic shock. Emerged evidence has shown that induction of trained immunity triggers a much stronger inflammatory response in adult monocytes/macrophages, thereby conferring protection against microbial infection. Methods This study was carried out to examine whether trained immunity is inducible and exerts its protection against microbial sepsis in neonates. Results Induction of trained immunity by Bacillus Calmette-Guerin (BCG) plus bacterial lipoprotein (BLP) protected neonatal mice against cecal slurry peritonitis-induced polymicrobial sepsis, and this protection is associated with elevated circulating inflammatory cytokines, increased neutrophil recruitment, and accelerated bacterial clearance. In vitro stimulation of neonatal murine macrophages with BCG+BLP augmented both inflammatory response and antimicrobial activity. Notably, BCG+BLP stimulation resulted in epigenetic remodeling characterized by histone modifications with enhanced H3K4me3, H3K27Ac, and suppressed H3K9me3 at the promoters of the targeted inflammatory and antimicrobial genes. Critically, BCG+BLP stimulation led to a shift in cellular metabolism with increased glycolysis, which is the prerequisite for subsequent BCG+BLP-triggered epigenetic reprogramming and augmented inflammatory response and antimicrobial capacity. Conclusion These results illustrate that BCG+BLP induces trained immunity in neonates, thereby protecting against microbial infection by boosting both inflammatory and antimicrobial responses.en_US
dc.language.isoenen_US
dc.rights© 2022 Zhou et al.
dc.rightsAttribution-NonCommercial 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/*
dc.subjectantimicrobial activityen_US
dc.subjectEpigenetic reprogrammingen_US
dc.subjectinflammatory responseen_US
dc.subjectintracellular metabolic rewiringen_US
dc.subjectneonatal sepsisen_US
dc.subjecttrained immunityen_US
dc.titleInduction of Trained Immunity Protects Neonatal Mice Against Microbial Sepsis by Boosting Both the Inflammatory Response and Antimicrobial Activity.en_US
dc.typeArticleen_US
dc.identifier.journalJournal of inflammation researchen_US
dc.source.journaltitleJournal of inflammation research
dc.source.volume15
dc.source.beginpage3829
dc.source.endpage3845
refterms.dateFOA2024-07-19T09:03:55Z
dc.source.countryNew Zealand


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© 2022 Zhou et al.
Except where otherwise noted, this item's license is described as © 2022 Zhou et al.