1. BCG vaccination–induced emergency granulopoiesis provides rapid protection from neonatal sepsis
- Author
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Bing Cai, James L. Wynn, Aaron C Liu, Kristina Lindberg Larsen, Joe Huang, Tobias R. Kollmann, Ofer Levy, Peter Aaby, Scott J. Tebbutt, Morten Bjerregaard-Andersen, Christine Stabell Benn, Lilica Sanca, Casey P. Shannon, Natallia Varankovich, Freddy Francis, Daniel He, Christian N. Golding, Beate Kampmann, Byron Brook, Frank Shann, Rym Ben-Othman, Rusung Tan, Danny Harbeson, Nelly Amenyogbe, Adrian K. Charles, Winnie Bao, and Frederik Schaltz-Buchholzer
- Subjects
Neonatal sepsis ,business.industry ,Vaccination ,Infant, Newborn ,General Medicine ,Granulocyte ,medicine.disease ,Systemic inflammation ,Granulopoiesis ,Article ,Hematopoiesis ,Granulocyte colony-stimulating factor ,Sepsis ,medicine.anatomical_structure ,Granulocyte Colony-Stimulating Factor ,Immunology ,medicine ,Humans ,Tumor necrosis factor alpha ,Neonatal Sepsis ,medicine.symptom ,business - 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.
- Published
- 2020