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

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

Science translational medicine (2020-05-08)

Byron Brook, Danny J Harbeson, Casey P Shannon, Bing Cai, Daniel He, Rym Ben-Othman, Freddy Francis, Joe Huang, Natallia Varankovich, Aaron Liu, Winnie Bao, Morten Bjerregaard-Andersen, Frederik Schaltz-Buchholzer, Lilica Sanca, Christian N Golding, Kristina Lindberg Larsen, Ofer Levy, Beate Kampmann, Rusung Tan, Adrian Charles, James L Wynn, Frank Shann, Peter Aaby, Christine S Benn, Scott J Tebbutt, Tobias R Kollmann, Nelly Amenyogbe

PMID32376769

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.

MATERIALS

Product Number

Brand

Product Description

L8274

Sigma-Aldrich

Lipopolysaccharides from Escherichia coli O26:B6, ≥10,000 EU/mg, purified by phenol extraction

22091

Millipore

Tryptic Soy Agar - Dehydrated Culture Media, NutriSelect^® Plus, powder, suitable for microbiology