Lactate's Role in Enhancing Innate Immune Defenses Through Training and Epigenetic Changes

Recent research highlights the significant role of lactate in shaping our body's innate immune response. The BCG vaccine, primarily used to prevent tuberculosis, is known not only for targeting specific pathogens but also for boosting overall immune readiness through a process called "trained immunity." This mechanism allows the innate immune system to respond more vigorously to various infections beyond its initial training.

A comprehensive study led by Radboud University Medical Center delves into how this training occurs at the cellular level. The team explains that innate immune cells must modify both their metabolic activity and gene transcription via epigenetic changes to store immune information effectively. Notably, these cells undergo epigenetic memory formation, enabling a faster and more robust response upon re-exposure to pathogens.

An intriguing aspect of this process involves lactate, a byproduct traditionally considered waste in energy metabolism. Researchers have uncovered that during immune training, cells consume more glucose and produce increased lactate. Recent evidence indicates that lactate is not merely a metabolic waste but also acts as an epigenetic regulator. It can bind to histones—proteins associated with DNA—and induce modifications known as histone lactylation. This modification likely influences gene expression, toggling genes involved in inflammation and immune responses.

The study further demonstrates the molecular capacity of lactate to function as a "trainer" of the innate immune system. In vaccinated individuals, elevated lactate levels correlated with increased cytokine production and activation of immune-related genes, which persisted for at least three months. When lactate production was inhibited, the trained immune response diminished, indicating lactate's crucial role in immune memory formation.

Overall, this emerging understanding positions lactate as a key molecule bridging metabolism and epigenetics in immune regulation. It opens new avenues for therapeutic strategies that could enhance immune training and improve resistance to respiratory infections, leveraging metabolic pathways to bolster innate defenses.