BCG vaccination potentiates oxidative phosphorylation in neonatal myeloid-derived suppressor cells

Bacillus Calmette-Guérin (BCG) vaccination has well-documented off-target effects in early life, but the underlying molecular mechanisms remain incompletely understood. This study investigated whether BCG reprograms neonatal myeloid-derived suppressor cells (MDSCs) through oxidative phosphorylation (OXPHOS). After neonatal mice received a subcutaneous injection of BCG or PBS, the effects of BCG exposure on splenic monocytic (M-) and polymorphonuclear (PMN-) MDSCs were assessed. BCG vaccination significantly increased the expression of OXPHOS-related genes (Ndufab1, Sdhd, Uqcrfs1, Cox4i) and mitochondrial oxidative activity in both MDSC subsets. Seahorse analysis revealed a higher oxygen consumption rate in BCG-exposed PMN-MDSCs. Functional assays showed that BCG impaired MDSC-mediated T-cell suppression, with oligomycin treatment partially able to restore this suppressive capacity. Together, these findings indicate that BCG-induced OXPHOS potentiation contributes to the loss of MDSC immunosuppressive function in neonatal mice, providing a molecular mechanism for the non-specific immunomodulatory effects of BCG vaccination early in life.