Journal
SCIENCE TRANSLATIONAL MEDICINE
Volume 12, Issue 542, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.aax4517
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Funding
- National Institute of Allergy and Infectious Diseases (NIAID) of the NIH [5U19AI118608-02]
- Telethon Kids
- Perth Children's Hospital Foundation
- Michael Smith Foundation for Health Research Career Investigator Award
- U.S. NIH/NIAID [1U01AI124284-01, HHSN272201400052C, HHSN272201800047C]
- internal Boston Children's Hospital award
- Medical Research Council, UK [MR/R005990/1, MC_UP_A900/1122, MC_UP_A900/115]
- NIH/NICHD [R01HD089939, R01HD097081]
- NIH/NIGMS [R01GM128452]
- CVIVA
- Danish National Research Foundation [DNRF108]
- Karen Elise Jensens Fond
- Augustinusfonden, Else og Mogens Wedell Wedellborgs Fond
- Fonden til Laegevidenskabens Fremme
- MRC [MR/R005990/2, MC_PC_17221, MR/R005990/1] Funding Source: UKRI
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Death from sepsis in the neonatal period remains a serious threat for millions. Within 3 days of administration, bacille Calmette-Guerin (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.
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