Journal article

BCG Vaccination in Humans Elicits Trained Immunity via the Hematopoietic Progenitor Compartment

Branko Cirovic, L Charlotte J de Bree, Laszlo Groh, Bas A Blok, Joyce Chan, Walter JFM van der Velden, MEJ Bremmers, Reinout van Crevel, Kristian Handler, Simone Picelli, Jonas Schulte-Schrepping, Kathrin Klee, Marije Oosting, Valerie ACM Koeken, Jakko van Ingen, Yang Li, Christine S Benn, Joachim L Schultze, Leo AB Joosten, Nigel Curtis Show all

Cell Host & Microbe | CELL PRESS | Published : 2020

Abstract

Induction of trained immunity by Bacille-Calmette-Guérin (BCG) vaccination mediates beneficial heterologous effects, but the mechanisms underlying its persistence and magnitude remain elusive. In this study, we show that BCG vaccination in healthy human volunteers induces a persistent transcriptional program connected to myeloid cell development and function within the hematopoietic stem and progenitor cell (HSPC) compartment in the bone marrow. We identify hepatic nuclear factor (HNF) family members 1a and b as crucial regulators of this transcriptional shift. These findings are corroborated by higher granulocyte numbers in BCG-vaccinated infants, HNF1 SNP variants that correlate with train..

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Grants

Awarded by ERC


Awarded by Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy


Awarded by Emmy Noether research grant


Awarded by Danish National Research Foundation


Awarded by European Union


Funding Acknowledgements

This study was supported by an ERC advanced grant (#833247) and a Spinoza grant of the Netherlands Organization for Scientific Research (to M.G.N.). Additionally, this study was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy - EXC2151 - 390873048 (to M.G.N., A.S., and J.L.S.), and an Emmy Noether research grant (SCHL2116/1 to A.S.). CVIVA is established with a grant from the Danish National Research Foundation (DNRF108). Additionally, this project has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement no 733100 (to J.L.S.).