TY - JOUR
T1 - BCG vaccination-induced emergency granulopoiesis provides rapid protection from neonatal sepsis
AU - The EPIC Consortium
AU - Brook, Byron
AU - Harbeson, Danny J.
AU - Shannon, Casey P.
AU - Cai, Bing
AU - He, Daniel
AU - Ben-Othman, Rym
AU - Francis, Freddy
AU - Huang, Joe
AU - Varankovich, Natallia
AU - Liu, Aaron
AU - Bao, Winnie
AU - Bjerregaard-Andersen, Morten
AU - Schaltz-Buchholzer, Frederik
AU - Sanca, Lilica
AU - Golding, Christian N.
AU - Larsen, Kristina Lindberg
AU - Levy, Ofer
AU - Kampmann, Beate
AU - Tan, Rusung
AU - Charles, Adrian
AU - Wynn, James L.
AU - Shann, Frank
AU - Aaby, Peter
AU - Benn, Christine S.
AU - Tebbutt, Scott J.
AU - Kollmann, Tobias R.
AU - Amenyogbe, Nelly
AU - Lee, Amy H.
AU - Bennike, Tue B.
AU - Diray-Arce, Joann
AU - Idoko, Olubukola
AU - Pomat, William S.
AU - van Haren, Simon
AU - Cox, Momoudou
AU - Darboe, Alansana
AU - Falsafi, Reza
AU - Hinshaw, Samuel H.
AU - Ndure, Jorjoh
AU - Njie-Jobe, Jainaba
AU - Pettengill, Matthew A.
AU - Marchant, Arnaud
AU - Richmond, Peter C.
AU - Ford, Rebecca
AU - Saleu, Gerard
AU - Masiria, Geraldine
AU - Matlam, John Paul
AU - Kirarock, Wendy
AU - Roberts, Elishia
AU - Malek, Mehrnoush
AU - Hancock, Robert E.W.
N1 - Publisher Copyright:
© 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
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 - Article
C2 - 32376769
AN - SCOPUS:85084387993
SN - 1946-6234
VL - 12
JO - Science Translational Medicine
JF - Science Translational Medicine
IS - 542
M1 - eaax4517
ER -