Bacillus Calmette-Guérin-induced trained immunity potentiates TH17 responses in vitro

Area of Science:

• Immunology
• Cell Biology

Background:

• Trained immunity amplifies innate immune responses independently of antigens.
• Macrophages are crucial for T cell activation, but their role in trained immunity's effect on T cells is understudied.

Purpose of the Study:

• To investigate how trained human primary macrophages influence T cell phenotype and function.
• To determine if trained immunity in macrophages modulates T cell activation.

Main Methods:

• Surface marker analysis of naive, β-glucan-, and BCG-trained macrophages.
• In vitro co-culture of T cells with autologous BCG-trained macrophages.
• Analysis of T cell responses, including cytokine production and surface markers, after BCG vaccination in human subjects.

Main Results:

• BCG-trained macrophages exhibited increased CD40, CD86, and MHC molecules.
• Co-culture with BCG-trained macrophages induced a TH17 cell bias, which was also observed post-BCG vaccination.
• TH17 skewing required direct cell-to-cell contact and was antigen-independent.
• Trained macrophages enhanced interferon-gamma and interleukin-17 production but did not shift T cells towards effector or memory phenotypes.

Conclusions:

• BCG-trained macrophages can modulate T cell function, promoting a TH17 phenotype.
• BCG-induced trained immunity may enhance innate immunity and also influence adaptive T cell immunity.