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

B Brook; DJ Harbeson; CP Shannon; B Cai; D He; R Ben-Othman; F Francis; J Huang; N Varankovich; A Liu; W Bao; M Bjerregaard-Andersen; F Schaltz-Buchholzer; L Sanca; CN Golding; KL Larsen; O Levy; B Kampmann; R Tan; A Charles; JL Wynn; F Shann; P Aaby; CS Benn; SJ Tebbutt; TR Kollmann; N Amenyogbe; AH Lee; TB Bennike; J Diray-Arce; O Idoko; WS Pomat; S van Haren; M Cox; A Darboe; R Falsafi; SH Hinshaw; J Ndure; J Njie-Jobe; MA Pettengill; A Marchant; PC Richmond; R Ford; G Saleu; G Masiria; JP Matlam; W Kirarock; E Roberts; M Malek; G Sanchez-Schmitz; A Singh; A Angelidou; KK Smolen; RR Brinkman; A Ozonoff; REW Hancock; AHJ van den Biggelaar; H Steen; D Vo; K Kraft; K McEnaney; S Vignolo

Journal article

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

B Brook, DJ Harbeson, CP Shannon, B Cai, D He, R Ben-Othman, F Francis, J Huang, N Varankovich, A Liu, W Bao, M Bjerregaard-Andersen, F Schaltz-Buchholzer, L Sanca, CN Golding, KL Larsen, O Levy, B Kampmann, R Tan, A 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

Grants

Awarded by UK Research and Innovation

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.