Protective effect of heat-inactivated Mycobacterium bovis applied intramuscularly is associated with enhanced lung immune response in caprine tuberculosis

Caprine tuberculosis (TB) causes a zoonotic disease with significant economic and health implications. However, excluding some regions, goat herds are not subjected to official TB eradication programs. Implementing vaccination protocols for this species could provide a complementary and effective control strategy against TB. We assessed the protective efficacy and immune response associated with a heat-inactivated Mycobacterium bovis ( M . bovis )-based immunostimulant (HIMB) applied intramuscularly against caprine pulmonary TB on 20 kid goats (10 immunized, 10 controls) naturally exposed to M . caprae infected goats for 10 months. TB-compatible lung lesions were assessed, alongside a local immune response analysis by immunohistochemistry of cell populations (Macrophages (MΦs), neutrophils, T, and B lymphocytes) and associated immune mediators (iNOS, TNF-α, IL-1α, IL-6, IFN-γ, TGF-β, IL-4). In the control group, 60% of the animals showed TB compatible lesions, compared with 40% of the immunized animals, which also showed a 78% reduction ( p  = 0.03) in the lesion severity score. Moreover, immunized animals showed a higher number of M1 MΦs ( p  = 0.03), producers of iNOS, as well as a higher expression of TNFα ( p  = 0.04) and IL-1α ( p  = 0.03). These mediators play a key role in the activation of a Th1-type cellular immune responses effective against mycobacteria, associated with a response of T lymphocytes expressing IFNγ, whose response was increased in the immunized group ( p  = 0.05). These results suggest that immunization with HIMB reduced the number and severity of TB-associated pulmonary lesions, which could be linked with an enhanced production of immune mediators with an essential role in the activation of MΦs with bactericidal functions.