Trained immunity epigenetics

Two papers on trained immunity, starting with a 2022 review:

“Live attenuated vaccines such as the Bacillus Calmette–Guérin, measles-containing vaccines, and the oral polio vaccine have been shown to reduce overall mortality beyond their effects attributable to the targeted diseases.

After an encounter with a primary stimulus, epigenetic and metabolic reprogramming of bone marrow progenitor cells and functional changes of tissue immune cell populations result in augmented immune responses against a secondary challenge. This process has been termed trained immunity.

Main epigenetic events during induction of trained immunity are:

  1. Chromosomal reorganization on the level of topologically associated domains;
  2. Induction of long noncoding RNA activity;
  3. Histone modifications and chromatin accessibility; and
  4. DNA (de)methylation.

trained immunity mechanisms

An epigenetic enzyme belonging to the lysine methyltransferase family, Set7, possesses vital function in β-glucan training of monocytes. When inhibited, trained immunity phenotype is diminished, while Set7 deficient mice cannot establish innate immune memory.

β-glucan is recognized by Dectin-1, and has been known to lead to a shift from oxidative phosphorylation (OXPHOS) to glycolysis as an ATP source. However, a more recent study reported an increase in both glycolysis and oxygen consumption following training, which signals a higher rate of OXPHOS. This discrepancy is explained by the difference in concentration of β-glucan used in the experiments.

Stopping vaccination with measles and polio once the pathogens are eradicated, or replacing live attenuated polio with inactivated polio, should be done with caution, as it may have a substantial impact on childhood mortality. Trained immunity may also represent an important new approach to improve current vaccines, or to develop novel vaccines that combine induction of classical adaptive immune memory and innate immune memory.” “Trained immunity: implications for vaccination”

Reference 34 was a 2020 study by two of the same coauthors that provided details on the above discrepancy:

“Findings presented by the current study suggest that the disparity in terms of the role of OXPHOS arises from the stimulatory dose of β-glucan [by intraperitoneal injection]. A β-glucan concentration of 1 μg/mL induces both glycolysis and OXPHOS, whereas a concentration of 10 μg/mL induces glycolysis but inhibits OXPHOS.” “The Set7 Lysine Methyltransferase Regulates Plasticity in Oxidative Phosphorylation Necessary for Trained Immunity Induced by β-Glucan”


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