TY - JOUR
T1 - BCG vaccination–induced emergency granulopoiesis provides rapid protection from neonatal sepsis
AU - The EPIC Consortium
PY - 2020/5/6
Y1 - 2020/5/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85084387993&partnerID=8YFLogxK
U2 - 10.1126/scitranslmed.aax4517
DO - 10.1126/scitranslmed.aax4517
M3 - Journal article
SN - 1946-6234
VL - 12
SP - eaax4517
JO - Science Translational Medicine
JF - Science Translational Medicine
IS - 542
M1 - eaax4517
ER -