Fatty acid desaturation and lipoxygenase pathways support trained immunity

Area of Science:

• Immunology
• Metabolic pathways
• Innate immune memory

Background:

• Infections and vaccines can induce long-term changes in innate immune cells, a phenomenon known as trained immunity.
• Trained immunity involves enhanced responses of innate immune cells, offering protection against subsequent challenges.

Purpose of the Study:

• To investigate the role of lipid mediators (LM) in Bacillus Calmette-Guérin (BCG)-induced trained immunity in human monocytes.
• To identify specific lipid metabolic pathways involved in the development and function of trained immunity.

Main Methods:

• Monocytes from healthy individuals were exposed to the BCG vaccine.
• Pharmacological and genetic approaches were used to assess the impact of lipid synthesis inhibition on trained immunity.
• Levels of lipid mediators and enzyme activity were measured using biochemical assays.

Main Results:

• BCG-vaccinated monocytes exhibited an increased biosynthesis of lipid mediators derived from long-chain polyunsaturated fatty acids (PUFA).
• Inhibition of long-chain PUFA synthesis and lipoxygenase-derived LM impaired BCG-induced trained immunity in human monocytes.
• Products of 12-lipoxygenase activity were elevated in monocytes post-BCG vaccination.

Conclusions:

• Lipid metabolic pathways, particularly those involving long-chain PUFA and lipoxygenase activity, are essential for BCG-induced trained immunity.
• Understanding these lipid pathways provides insights into trained immunity and potential therapeutic targets for modulating innate immune responses.