Metabolic Regulation in the Induction of Trained Immunity

Area of Science:

• Immunology
• Metabolic pathways
• Epigenetics

Background:

• The innate immune system possesses memory-like properties, known as trained immunity, enhancing responses to subsequent infections.
• This innate immune memory is maintained by epigenetic modifications influencing gene accessibility and transcription.
• Metabolic rewiring is closely linked to epigenetic alterations in trained immunity.

Purpose of the Study:

• To review metabolic pathways crucial for the induction and maintenance of trained immunity.
• To explore the role of metabolic pathways in specific cells, such as lung alveolar macrophages.
• To discuss the therapeutic potential of targeting innate immune cell metabolism.

Main Methods:

• Review of existing literature on metabolic pathways involved in trained immunity.
• Analysis of the interplay between epigenetics and metabolism in innate immune memory.
• Focus on key metabolic routes including glycolysis, oxidative phosphorylation, and amino/lipid metabolism.

Main Results:

• Glycolysis, oxidative phosphorylation, tricarboxylic acid cycle, and amino acid/lipid metabolism are central to trained immunity.
• These metabolic pathways establish innate immune memory in various cellular compartments, including lung alveolar macrophages.
• The intricate interplay of these pathways is essential for sustained innate immune memory.

Conclusions:

• Targeting metabolic programs in innate immune cells presents a promising therapeutic avenue.
• This strategy could be used to enhance immune responses in immunosuppressed individuals.
• It may also help mitigate excessive inflammation in hyperinflammatory conditions.