BCG immunization induced KLRG1+ NK cells show memory-like responses to mycobacterial and HIV antigens

Abstract The live-attenuated Bacille-Calmette-Guérin (BCG) vaccine is the only approved vaccine against Mycobacterium tuberculosis (MTB), offering broad protection against tuberculosis (TB) and other infectious diseases. ‘Trained immunity’, a process where innate immune cells develop memory-like features, is considered one of the BCG vaccine’s protective mechanisms. In this study, we investigated the effect of BCG vaccination on Natural Killer (NK) cells, a key subset of the innate immune system, and their ability to give rise to heterologous memory-like responses to HIV antigens. Here we found that BCG vaccine-induced KLRG1+ NK cells exhibit memory-like responses to both MTB and HIV antigens, as evidenced by their increased production of IFNγ upon exposure to MTB and HIV-gag antigens. This finding is of great importance, as co-infection with HIV and TB is highly relevant in Asia and Africa where BCG is administered. Understanding these responses is crucial for the development of more effective vaccines and therapeutics for both TB and HIV.