The vaccine against tuberculosis, BCG, has been shown to have several other protective non-specific effects. BCG vaccination in countries with a high burden of infectious diseases results in reduced mortality due to less lower respiratory infections and neonatal sepsis. BCG is also used in the treatment of bladder cancer.
Mihai Netea and colleagues have already shown before that vaccination with the BCG vaccine induces trained immunity; a non-specific memory within the innate immune system that makes monocytes and macrophages more pro-inflammatory, a process that is long-lasting and epigenetically regulated and could be the cause how BCG protects against other infectious diseases as well. In their current paper, Netea and colleagues describe how metabolic changes occur in BCG-trained monocytes and macrophages (e.g. upregulation of glycolysis) and that these metabolic changes are essential for induction of the trained phenotype of these cells. Moreover, these changes in metabolism are the result of epigenetic modifications, but interestingly the epigenetic changes are on their turn dependent on metabolic changes. Hence, showing a complex system where metabolism and epigenetics are intertwined as the molecular base of the induction of trained immunity by BCG.
This shows us important insights in how trained immunity works. By better understanding this non-specific memory of the innate immune system, we can think of ways to use trained immunity as immunotherapy in patients with inherited or acquired immunodeficiencies or vulnerable individuals, such as neonates or the elderly.
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