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

Overview

Journal Cell Host Microbe

Publisher Cell Press

Specialties Infectious Diseases
Microbiology

Date 2020 Jun 17

PMID 32544459

Citations 210

Authors

Branko Cirovic

L Charlotte J de Bree

Laszlo Groh

Bas A Blok

Joyce Chan

Walter J F M van der Velden

M E J Bremmers

Reinout van Crevel

Kristian Handler

Simone Picelli

Jonas Schulte-Schrepping

Kathrin Klee

Marije Oosting

Valerie A C M Koeken

Jakko van Ingen

Yang Li

Christine S Benn

Joachim L Schultze

Leo A B Joosten

Nigel Curtis

Mihai G Netea

Andreas Schlitzer

Affiliations

Soon will be listed here.

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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