Immunity · 2024
Multi-omics analysis of innate and adaptive responses to BCG vaccination reveals epigenetic cell states that predict trained immunity.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Moorlag Simone J C F M, Folkman Lukas, Ter Horst Rob, Krausgruber Thomas, Barreca Daniele, Schuster Linda C, Fife Victoria, Matzaraki Vasiliki, Li Wenchao, Reichl Stephan, Mourits Vera P, Koeken Valerie A C M, de Bree L Charlotte J, Dijkstra Helga, Lemmers Heidi, van Cranenbroek Bram, van Rijssen Esther, Koenen Hans J P M, Joosten Irma, Xu Cheng-Jian, Li Yang, Joosten Leo A B, van Crevel Reinout, Netea Mihai G, Bock Christoph
Аннотация
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.