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BCG vaccination reprograms the function of myeloid cells and aggravates necrotizing enterocolitis in neonates

ABSTRACT: Bacillus Calmette–Guérin (BCG) vaccination immediately after birth provides overall protection against immune disorders in healthy infants. However, for vulnerable infants such as preterm or low birth weights, delayed BCG vaccination is usually recommended. The mechanism underlying this clinical application remains obscure. Here we reported that BCG vaccination abrogated the transitory appearance of immunosuppressive myeloid cells in neonatal mice, that is myeloid-derived suppressor cells (MDSCs) represented as the important immunoprotection against inflammatory diseases in early life. A combination of single-cell transcriptome, metabolite profiling, and functional analysis revealed that the upregulation of mTOR/HIF1a signaling and the enhanced glycolysis explained the underlying mechanism. Consequently, BCG vaccination significantly exacerbated the severity of necrotizing enterocolitis (NEC), a common clinical emergency primarily affecting preterm or low birth weight infants. Adoptive transfer of MDSCs or pharmalogical inhibition of glycolysis or mTOR signaling efficiently relieved the severity of NEC upon BCG vaccination. These observations suggest that BCG may diminish the protective mechanism of myeloid cells and enhances the susceptibility of NEC in vulnerable neonates.

ORGANISM(S): Mus musculus

PROVIDER: GSE234153 | GEO | 2023/06/12

REPOSITORIES: GEO

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