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BCG vaccination-induced emergency granulopoiesis provides rapid protection from neonatal sepsis

We found that BCG, in a mouse model of neonatal polymicrobial sepsis, induced granulocyte colony-stimulating factor (G-CSF) within hours of administration

Citation:
Brook B, Harbeson DJ, Shannon CP, Cai B, He D, Ben-Othman R, ..., Kollmann TR, Amenyogbe N. BCG vaccination-induced emergency granulopoiesis provides rapid protection from neonatal sepsis. Science translational medicine. 2020;12(542)

Abstract:
Death from sepsis in the neonatal period remains a serious threat for millions. Within 3 days of administration, bacille Calmette-Guérin (BCG) vaccination can reduce mortality from neonatal sepsis in human newborns, but the underlying mechanism for this rapid protection is unknown. We found that BCG was also protective in a mouse model of neonatal polymicrobial sepsis, where it induced granulocyte colony-stimulating factor (G-CSF) within hours of administration. This was necessary and sufficient to drive emergency granulopoiesis (EG), resulting in a marked increase in neutrophils. This increase in neutrophils was directly and quantitatively responsible for protection from sepsis. Rapid induction of EG after BCG administration also occurred in three independent cohorts of human neonates.