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Evolution and development of innate immune memory.

Maziar Divangahi^1,2,3, Eva Kaufmann^1,4,5

¹Meakins-Christie Laboratories, Department of Medicine, McGill University, Montreal, Canada.

Science Immunology

|July 3, 2026

Summary

This summary is machine-generated.

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Linking metabolic and epigenetic changes in immune tolerance.

Proceedings of the National Academy of Sciences of the United States of America·2024

Innate immune memory, or trained immunity, involves epigenetic and metabolic changes in immune cells. This review explores how life stages and environmental exposures shape trained immunity, impacting health and inflammation.

Area of Science:

Immunology
Epigenetics
Life Sciences

Background:

Innate immune memory, termed trained immunity, involves epigenetic and metabolic reprogramming of innate immune cells and progenitors.
This phenomenon is conserved across eukaryotes and functions dynamically throughout life phases.

Purpose of the Study:

To review how the exposome shapes innate immune trajectories across the lifespan.
To discuss implications for trained immunity-based strategies to mitigate maladaptive inflammation.

Main Methods:

Review of existing literature on innate immune memory, epigenetics, metabolism, and aging.
Analysis of life-phase-specific adaptations and disruptions in trained immunity.

Main Results:

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Innate immune memory programming shifts from tolerogenic in early life to integrated with adaptive immunity in adulthood.

Aging disrupts this integration, leading to immunosenescence and inflammaging due to cumulative maladaptive training.

Conclusions:

The exposome continuously influences innate immune development and function throughout life.
Understanding these dynamics is crucial for developing interventions against age-related inflammatory diseases.