How innate immune memory rewires cell metabolism

Trained immunity is a form of memory in the innate immune system. Unlike classical immune memory, which is specific to one pathogen, trained immunity makes immune cells broadly more alert. They respond faster and stronger to a subsequent challenge, even if that challenge differs from the original one.

Researchers published a review article in the journal eLife that separates two types of metabolic changes. The first type occurs during initial activation and leads to changes in epigenetic marks (adjustments in how genes are switched on or off, without changing the DNA sequence itself). The second type follows later, as a consequence of those epigenetic changes, keeping the immune cell in a heightened state of readiness. The study emphasizes that not all substances that activate metabolism also produce trained immunity.

Why this matters for aging

As we age, the innate immune system changes. Chronic low-grade inflammation, known as inflammaging, is partly driven by immune cells that remain activated too long or too broadly. Trained immunity could contribute both positively and negatively: a well-calibrated system protects, but an overactive one contributes to tissue damage.

The distinction the authors draw between two phases of metabolic change is relevant for longevity research. If we better understand which metabolic signals activate the desired immune memory, and which trigger harmful chronic activation, more targeted interventions become conceivable.

Monocytes and macrophages as study subjects

The research focuses specifically on monocytes and macrophages, two types of white blood cells central to the innate immune system. In these cells, the changes in metabolism and epigenetic activity are most clearly visible following a training stimulus. Whether similar processes occur in other immune cell types remains an open question for future research.

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