BCG-Induced Immune Training: Interplay between Trained Immunity and Emergency Granulopoiesis

Bacille Calmette-Guérin (BCG) is the most commonly administered vaccine in human history. The medical application of BCG extends far beyond the fight against tuberculosis. Despite its stellar medical record over 100 years, insight into how BCG provides this vast range of benefits is largely limited, both for its pathogen-specific (tuberculosis) as well as pathogen-agnostic (other infections, autoimmunity, allergies, and cancer) effects. Trained immunity and emergency granulopoiesis have been identified as mediating BCG's pathogen-agnostic effects, for which some of the molecular mechanisms have been delineated. Upon review of the existing evidence, we postulate that emergency granulopoiesis and trained immunity are a continuum of the same effect cascade. In this context, we highlight that BCG's pathogen-agnostic benefits could be optimized by taking advantage of the age of the recipient and route of BCG administration.