Mucosal exposure to non-tuberculous mycobacteria elicits B-cell mediated protection against pulmonary tuberculosis

Bacille Calmette Guerin (BCG) is the only licensed vaccine against Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB) disease. However, BCG has limited efficacy, necessitating the development of better vaccines. Non-tuberculous mycobacteria (NTM), a distinct lineage from Mtb, are opportunistic pathogens present in the environment. TB endemic countries experience higher exposure to NTM, but previous studies have not elucidated the relationship between NTM exposure and BCG efficacy. Therefore, we developed a mouse model (BCG+NTM) that mimics human BCG vaccination at an early stage and continuous NTM exposure via the oral route, including during TB infection. Our results show that BCG+NTM mice had improved protection against pulmonary TB correlating with increased pulmonary influx of B-cells, higher titers of anti-Mtb IgA and IgG antibodies in serum and airways, compared to mice vaccinated with BCG alone. Notably, the lungs of BCG+NTM mice developed B-cell aggregates expressing markers of germinal center formation as determined by spatial transcriptomics. We conclude a direct correlation between NTM exposure and protection from TB, with B-cells playing a crucial role. This is a spatial transcriptomics dataset generated using 10X Visium kit for FFPE tisues. There are four groups: Saline (control group); BCG (mice vaccinated with Bacille Calmette Geurin vaccine and infected with Mycobacterium tuberculosis); NTM (Mice exposed to 1X10^5 CFU/mL Myobacterium avium via drinking water and infected with Mycobacterium tuberculosis), and BCG+NTM (Mice vaccinated with BCG, exposed to 1X10^5 CFU/mL Myobacterium avium via drinking water and infected with Mycobacterium tuberculosis).