BCG-induced trained immunity potentiates TH17 responses in vitro.

Trained immunity amplifies innate immune responses in an antigen-independent manner. This study explored the ability of trained human primary macrophages to modulate the phenotype and function of T cells. Macrophages play an important role in antigen presentation, resulting in T-cell activation and antigen-specific clonal expansion; however, few studies have investigated whether trained immunity induction in macrophages modulates T cell activation. Here, through surface marker analysis of naive, β-glucan-, and BCG-trained macrophages, we identified eight distinct macrophage clusters following trained immunity induction. One of these populations showed an increase in surface activation markers CD40 and CD86, as well as MHC molecules. In vitro co-culture of T cells with autologous BCG-trained macrophages resulted in a skewing towards TH17 cells. We also observed an increase in TH17 percentage after BCG vaccination of human subjects. The bias towards TH17 triggered by trained macrophages required direct T cell to macrophage contact. Trained macrophages potentiated TH17 skewing independently of the antigen presented. While co-cultures of T cells and BCG-trained macrophages responded with higher production of interferon (IFN)-γ and interleukin (IL)-17 after stimulation, no clear shifts towards effector or memory T cells were observed. In conclusion, this study provides evidence that BCG-trained macrophages can modulate T cell function towards a TH17 phenotype, suggesting that BCG-induced trained immunity has the potential to enhance not only innate immune responses but also to modify adaptive T cell immunity.

© The Author(s) 2025. Published by Oxford University Press on behalf of Society for Leukocyte Biology.

PMID: 40879531