BCG vaccination-induced emergency granulopoiesis provides rapid protection from neonatal sepsis.
Byron BrookDanny J HarbesonCasey P ShannonBing CaiDaniel HeRym Ben-OthmanFreddy FrancisYue Zhou HuangNatallia VarankovichAaron LiuWinnie BaoMorten Bjerregaard-AndersenFrederik Schaltz-BuchholzerLilica SancaChristian N GoldingKristina Lindberg LarsenOfer LevyBeate Kampmannnull nullRusung TanAdrian K CharlesJames Lawrence WynnFrank ShannPeter AabyChristine Stabell BennScott J TebbuttTobias R KollmannNelly AmenyogbePublished in: Science translational medicine (2021)
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.
Keyphrases
- septic shock
- acute kidney injury
- intensive care unit
- endothelial cells
- mouse model
- high glucose
- emergency department
- healthcare
- pregnant women
- loop mediated isothermal amplification
- cardiovascular disease
- drug induced
- cardiovascular events
- oxidative stress
- peripheral blood
- coronary artery disease
- gestational age
- muscle invasive bladder cancer