Mycobacterium avium via oral route provide enhanced protection against pulmonary tuberculosis: An essential role of B cells and germinal centers

Abstract Human tuberculosis (TB) is caused mainly by Mycobacterium tuberculosis (Mtb) and represents an enormous challenge to global health because of the inadequacy of currently available drugs and vaccines. The most common clinical manifestation is pulmonary TB, and the Bacille Calmette Guerin (BCG) is the only licensed vaccine for protection against TB; however, its efficacy is highly variable. Today at least 52 countries have reported MDR-TB and XDR-TB cases which cannot be cured or contained by current TB therapy. Thus, there is an urgent need to develop new therapies/vaccines that effectively prevent or cure TB. In the last decade, lymphoid follicles (LFs) having ectopic GCs (eGC) have been identified in the lungs of Mtb infected animals and humans; however, a mechanism of its formation and role has not been adequately characterized. Our studies found that mice vaccinated with BCG and exposed to Mycobacterium avium [a non-tuberculous mycobacterium (NTM)] via drinking water provide long-term protection from pulmonary TB than BCG alone as determined by reduced Mtb bacterial burden and inflammatory progression of infection. Interestingly, these mice also developed eGC in the lungs and have increased B cells, anti-Mtb cell lysate specific IgA, and IgG antibodies. These findings suggest that NTM and B cells play a critical role in generating protective immunity against pulmonary Mtb infection, and the formation of eGC in these mice is a crucial factor in this improved immunity. Investigating the mechanism of eGC formation and the role of NTM and B cells in its stimulation is an important question to understand TB pathogenesis and to develop effective vaccines and therapies. Supported by NIH/NIAID - 1R01AI127475-01AI, Colorado State University's MIP research team grant