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

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

Journal article

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

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 Show all

Science Translational Medicine | AMER ASSOC ADVANCEMENT SCIENCE | Published : 2020

DOI: 10.1126/scitranslmed.aax4517

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 induc..

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University of Melbourne Researchers

Frank Shann Author Paediatrics Royal Children's Hospital

Grants

Awarded by National Institute of Allergy and Infectious Diseases (NIAID) of the NIH

Awarded by U.S. NIH/NIAID

Awarded by Medical Research Council, UK

Awarded by NIH/NICHD

Awarded by NIH/NIGMS

Awarded by Danish National Research Foundation

Funding Acknowledgements

This work was in part supported by the National Institute of Allergy and Infectious Diseases (NIAID) of the NIH as part of the Human Immunology Project Consortium under 5U19AI118608-02. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. T.K.'s laboratory was supported by Telethon Kids and the Perth Children's Hospital Foundation, as well as a Michael Smith Foundation for Health Research Career Investigator Award. The Precision Vaccines Laboratory (directed by O.L.) is supported by the following U.S. NIH/NIAID awards: Molecular Mechanisms of Combination Adjuvants (1U01AI124284-01), Adjuvant Discovery Program (contract no. HHSN272201400052C), Adjuvant Development Program (contract no. HHSN272201800047C), and an internal Boston Children's Hospital award. B.K. is supported by funding from the Medical Research Council, UK (MR/R005990/1 and MC_UP_A900/1122, MC_UP_A900/115). J.L.W. is supported by NIH/NICHD (R01HD089939 and R01HD097081) and NIH/NIGMS (R01GM128452). The BCGIMED study was supported by CVIVA and the Danish National Research Foundation (DNRF108), as well as the Karen Elise Jensens Fond, the Augustinusfonden, Else og Mogens Wedell Wedellborgs Fond, and the Fonden til Laegevidenskabens Fremme.