BCG Vaccination in Humans Elicits Trained Immunity via the Hematopoietic Progenitor Compartment.
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Authors
Cirovic, Brankode Bree, L Charlotte J
Groh, Laszlo
Blok, Bas A
Chan, Joyce
van der Velden, Walter J F M
Bremmers, M E J
van Crevel, Reinout
Händler, Kristian
Picelli, Simone
Schulte-Schrepping, Jonas
Klee, Kathrin
Oosting, Marije
Koeken, Valerie A C M
van Ingen, Jakko
Li, Yang
Benn, Christine S
Schultze, Joachim L
Joosten, Leo A B
Curtis, Nigel
Netea, Mihai G
Schlitzer, Andreas
Issue Date
2020-06-09
Metadata
Show full item recordAbstract
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.Citation
Cell Host Microbe. 2020;S1931-3128(20)30296-1. doi:10.1016/j.chom.2020.05.014.Affiliation
CiiM, Zentrum für individualisierte Infektionsmedizin, Feodor-Lynen-Str.7, 30625 Hannover.Publisher
Elsevier (Cell Press)Journal
Cell host & microbePubMed ID
32544459PubMed Central ID
PMC7295478Additional Links
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295478/Type
ArticleLanguage
enEISSN
1934-6069ae974a485f413a2113503eed53cd6c53
10.1016/j.chom.2020.05.014
Scopus Count
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- Creative Commons
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 4.0 International
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