The immune system can work in two ways: the innate immune system reacts to any foreign invaders that are identified by immune cells that look for such pathogens; but the acquired or adaptive immune system responds to an infection that it has encountered before, and now 'remembers.' Vaccines can help train the acquired immune system, so it has such a memory of an infection, without the body needing to actually be infected.
The Bacille Calmette-Guérin (BCG) vaccine can protect an individual from tuberculosis, and it can also induce immunity against some other respiratory infections too. This vaccine can boost the adaptive immune system, and scientists have now shown that a molecule known as lactate is involved in this process. The findings have been reported in Cell.
Researchers wanted to know how exactly the BCG vaccine reduced infant mortality by lowering the risk of other respiratory infections and heightening innate immune defenses.
The researchers determined that innate immune cells alter genetic activity through epigenetic mechanisms when they are exposed to the BCG vaccine. Epigenetics refers to things that can influence gene expression, but without altering the genetic code; these changes might involve structural shifts, or chemical tags, for example. The BCG vaccine also induces metabolic changes in innate immune cells. So innate immune cells are aging through changes that are similar to what is seen in trained immune cells, creating more efficient cells after BCG vaccine exposure.
Innate immune cells that are 'trained' in this way use more glucose and generate more lactate.
"Until recently, lactate was seen as a waste product of energy production, without any further function. About some years ago, that slowly changed. In fact, there is increasing evidence that lactate can bind to proteins regulating DNA packaging, called histones, and induce an epigenetic modification known as histone lactylation," explained first study author Athanasios Ziogas, of Radboud University Medical Center (Radboudumc).
"According to recent research, this process may even be involved in switching genes on or off. That raises the question of whether lactate might play a role in the epigenetic regulation of trained immunity."
The researchers found that in healthy human volunteers, there was a connection between the production of lactate, and the responses to immune signals in innate immune cells.
There were also epigenetic changes in DNA, which triggered certain genes related to inflammatory processes in people who were exposed to the BCG vaccine. These changes lasted for at least three months. The inhibition of lactate impaired immune training, so lactate seems to have a direct effect on innate immunity that promotes trained immunity.
"Thus, lactate seems to be a molecular trainer of our innate defenses," added corresponding study author Mihai Netea of Radboudumc
Sources: Radboud University, Cell