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

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    Author
    Cirovic, B; de Bree, LCJ; Groh, L; Blok, BA; Chan, J; van der Velden, WJFM; Bremmers, MEJ; van Crevel, R; Handler, K; Picelli, S; ...
    Date
    2020-08-12
    Source Title
    Cell Host and Microbe
    Publisher
    CELL PRESS
    University of Melbourne Author/s
    Curtis, Richard
    Affiliation
    Paediatrics (RCH)
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    Document Type
    Journal Article
    Citations
    Cirovic, B., de Bree, L. C. J., Groh, L., Blok, B. A., Chan, J., van der Velden, W. J. F. M., Bremmers, M. E. J., van Crevel, R., Handler, K., Picelli, S., Schulte-Schrepping, J., Klee, K., Oosting, M., Koeken, V. A. C. M., van Ingen, J., Li, Y., Benn, C. S., Schultze, J. L., Joosten, L. A. B. ,... Schlitzer, A. (2020). BCG Vaccination in Humans Elicits Trained Immunity via the Hematopoietic Progenitor Compartment. CELL HOST & MICROBE, 28 (2), pp.322-+. https://doi.org/10.1016/j.chom.2020.05.014.
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    URI
    http://hdl.handle.net/11343/254502
    DOI
    10.1016/j.chom.2020.05.014
    Open Access URL
    Published version
    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 trained immunity, and elevated serum concentrations of the HNF1 target alpha-1 antitrypsin. Additionally, transcriptomic HSPC remodeling was epigenetically conveyed to peripheral CD14+ monocytes, displaying an activated transcriptional signature three months after BCG vaccination. Taken together, transcriptomic, epigenomic, and functional reprogramming of HSPCs and peripheral monocytes is a hallmark of BCG-induced trained immunity in humans.

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