Contrary to the claims of anti-vaccine campaigners, the tuberculosis vaccine not only saves lives from what used to be called consumption, it provides protection against a host of other diseases. Now, evidence has been produced to explain this strange, albeit welcome, phenomenon. The work challenges some theories about how aspects of the immune system work and brings an opportunity to harness this effect to protect us against diseases more efficiently.
Bacillus Calmette-Guerin (BCG) is the most widely used vaccine in the world, although it is not part of the standard schedule in nations where the Mycobacterium tuberculosis bacterium has been controlled in other ways. Its efficiency against tuberculosis is well short of 100 percent, but its true level of protection is debated. Surprisingly, however, it has been shown to provide limited protection against unrelated conditions as diverse as neonatal sepsis, leishmaniasis, warts, and even some cancers.
A study published in Cell Reports reveals evidence that this protection is a consequence of an increase in monocytes, a type of white blood cell that is part of what is called the innate immune system. Previous research had demonstrated the benefits of BCG in mice that lack certain immune system components, narrowing the potential paths that might be involved, but this is the first work to definitively identify the role of monocytes.
Exposure to BCG in both humans and mice boosts the process where glucose is converted to pyruvate, releasing energy. Oxygen consumption also increases, as does glutamine metabolism to a lesser extent. Collectively, these boost the capacity of immune cells to recognize and fight pathogens they have previously encountered, a process known as trained immunity.
"The implications of these findings are double: On the one hand, we have uncovered new biological interactions that link cellular metabolism with immune responses, and on the other hand, we have opened the door for new therapeutic approaches in which metabolism modulators modulate innate immune responses and can serve as potential novel immunotherapies," said senior author Professor Mihai Netea of Radboud University Medical Center, Netherlands.
The monocyte changes are a form of epigenetic reprogramming, where environmental circumstances modify the extent to which genes are expressed, making the effect long lasting.
"These findings change the concept that the innate immune system cannot adapt in the long-term after an infection or vaccination," Netea said. "The whole concept that the function of innate immune cells can change in a stable way, for example, being improved by certain vaccines such as BCG, is a paradigm shift in immunology, as until not too long ago it was assumed that only the adaptive immune system can adapt to previous infections or vaccinations."
Netea stressed that stimulating trained immunity in more controlled ways will take years of further research.
