BCG vaccination induces innate immune memory in γδ T cells in humans.

Abstract

Bacillus Calmette-Guérin vaccine is well known for inducing trained immunity in myeloid and natural killer cells, which can explain its cross-protective effect against heterologous infections. Although displaying functional characteristics of both adaptive and innate immunity, γδ T-cell memory has been only addressed in a pathogen-specific context. In this study, we aimed to determine whether human γδ T cells can mount trained immunity and therefore contribute to the cross-protective effect of the Bacillus Calmette-Guérin vaccine. We investigated in vivo induction of innate memory in γδ T cells by Bacillus Calmette-Guérin vaccination in healthy human volunteers by combining single-cell RNA sequencing technology with immune functional assays. The total number of γδ T cells and membrane markers of activation was not influenced by Bacillus Calmette-Guérin vaccination. In contrast, Bacillus Calmette-Guérin changed γδ T cells' transcriptional programs and increased their responsiveness to heterologous bacterial and fungal stimuli, including lipopolysaccharide and Candida albicans, as simultaneously characterized by higher tumor necrosis factor and interferon γ production, weeks after vaccination. Human γδ T cells in adults display the potential to develop a trained immunity phenotype after Bacillus Calmette-Guérin vaccination.

• Authors: Tsz K Suen, Simone J C F M Moorlag, Wenchao Li, L Charlotte J de Bree, Valerie A C M Koeken, Vera P Mourits, Helga Dijkstra, Heidi Lemmers, Jaydeep Bhat, Cheng-Jian Xu, Leo A B Joosten, Joachim L Schultze, Yang Li, Katarzyna Placek, Mihai G Netea
• Journal: Journal of leukocyte biology (J Leukoc Biol) Vol. 115 Issue 1 Pg. 149-163 (01 05 2024) ISSN: 1938-3673 [Electronic] England
• PMID: 37672677 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2023. Published by Oxford University Press on behalf of Society for Leukocyte Biology.

Chemical References

• BCG Vaccine
• Interferon-gamma

Topics

• Adult
• Humans
• BCG Vaccine
• Trained Immunity
• Interferon-gamma
• Mycobacterium bovis
• Immunity, Innate
• Vaccination