Multi-omics analysis of innate and adaptive responses to BCG vaccination reveals epigenetic cell states that predict trained immunity

Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved..

Immune responses are tightly regulated yet highly variable between individuals. To investigate human population variation of trained immunity, we immunized healthy individuals with Bacillus Calmette-Guérin (BCG). This live-attenuated vaccine induces not only an adaptive immune response against tuberculosis but also triggers innate immune activation and memory that are indicative of trained immunity. We established personal immune profiles and chromatin accessibility maps over a 90-day time course of BCG vaccination in 323 individuals. Our analysis uncovered genetic and epigenetic predictors of baseline immunity and immune response. BCG vaccination enhanced the innate immune response specifically in individuals with a dormant immune state at baseline, rather than providing a general boost of innate immunity. This study advances our understanding of BCG's heterologous immune-stimulatory effects and trained immunity in humans. Furthermore, it highlights the value of epigenetic cell states for connecting immune function with genotype and the environment.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:57

Enthalten in:

Immunity - 57(2024), 1 vom: 09. Jan., Seite 171-187.e14

Sprache:

Englisch

Beteiligte Personen:

Moorlag, Simone J C F M [VerfasserIn]
Folkman, Lukas [VerfasserIn]
Ter Horst, Rob [VerfasserIn]
Krausgruber, Thomas [VerfasserIn]
Barreca, Daniele [VerfasserIn]
Schuster, Linda C [VerfasserIn]
Fife, Victoria [VerfasserIn]
Matzaraki, Vasiliki [VerfasserIn]
Li, Wenchao [VerfasserIn]
Reichl, Stephan [VerfasserIn]
Mourits, Vera P [VerfasserIn]
Koeken, Valerie A C M [VerfasserIn]
de Bree, L Charlotte J [VerfasserIn]
Dijkstra, Helga [VerfasserIn]
Lemmers, Heidi [VerfasserIn]
van Cranenbroek, Bram [VerfasserIn]
van Rijssen, Esther [VerfasserIn]
Koenen, Hans J P M [VerfasserIn]
Joosten, Irma [VerfasserIn]
Xu, Cheng-Jian [VerfasserIn]
Li, Yang [VerfasserIn]
Joosten, Leo A B [VerfasserIn]
van Crevel, Reinout [VerfasserIn]
Netea, Mihai G [VerfasserIn]
Bock, Christoph [VerfasserIn]

Links:

Volltext

Themen:

BCG Vaccine
BCG vaccination
Bioinformatics
Chromatin profiling
Computational epigenomics
Epigenetic cell states
Genomics
Journal Article
Systems immunology
Trained immunity

Anmerkungen:

Date Completed 12.01.2024

Date Revised 12.01.2024

published: Print

Citation Status MEDLINE

doi:

10.1016/j.immuni.2023.12.005

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM366894382