BCG vaccination–induced emergency granulopoiesis provides rapid protection from neonatal sepsis
Byron Brook, Danny Harbeson, Casey P. Shannon, Bing Cai, Daniel He, Rym Ben-Othman, Freddy Francis, Yue Z. Huang, Natallia Varankovich, Aaron C. 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 Stabell Benn, Scott J. Tebbutt, Tobias R. Kollmann, Nelly Amenyogbe, Amy Huei‐Yi Lee, Tue Bjerg Bennike, Joann Diray‐Arce, Olubukola T. Idoko, William Pomat, Simon D. van Haren, Momoudou Cox, Alansana Darboe, Reza Falsafi, Samuel J. Hinshaw, Jorjoh Ndure, Jainaba Njie-Jobe, Matthew A. Pettengill, Arnaud Marchant, Peter Richmond, Rebecca Ford, G Saleu, Geraldine Masiria, John Paul Matlam, Wendy Kirarock, Elishia Roberts, Mehrnoush Malek, Guzman Sánchez‐Schmitz, Amrit Singh, Asimenia Angelidou, Kinga K. Smolen, Ryan R. Brinkman, Al Ozonoff, Robert E. W. Hancock, Anita H.J. van den Biggelaar, Hanno Steen, Diana Vo, Ken Kraft, Kerry McEnaney, Sofia M. Vignolo
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.