The Bacille Calmette–Guerin (BCG), the only vaccine against tuberculosis, remains the most commonly used vaccine worldwide. In addition to its effects on mycobacterial diseases, BCG also exerts beneficial non-specific effects ranging from protection against non-mycobacterial diseases, decreased incidence of allergic diseases, and treatment of certain malignancies. This is thought to be caused by potentiation of innate immune responses through epigenetic mechanisms, a process termed ‘trained immunity’. The process of trained immunity may also account for BCG-associated resistance to infection with Mycobacterium tuberculosis tuberculosis (also termed ‘early clearance’), and this could have important consequences for our quest for improving tuberculosis vaccination strategies.
BCG-induced trained immunity results in an increased in-vitro responsiveness of monocytes and macrophages, with effector functions such as cytokine production and reactive oxygen species release being increased upon secondary stimulation with non-related pathogens. The change in inflammatory profile and the underlying epigenetic changes are dependent on changes in cellular metabolism, and these metabolic changes are also epigenetically mediated, hence showing a complex interaction between immunometabolic pathways and epigenetic modifications in trained immunity.