Agulló-Ros, IreneMuñoz-Fernández, LeonorRoy, ÁlvaroBezos Garrido, JavierSevilla, Iker A.Moreno, InmaculadaGarrido, JosebaRodríguez Bertos, Antonio ManuelDomínguez, MercedesJuste, RamónDomínguez Rodríguez, Lucas JoséGortázar, ChristianRisalde, María A.2025-11-252025-11-252025Agulló-Ros, I., Muñoz-Fernández, L., Roy, Á., Bezos, J., Sevilla, I. A., Moreno, I., Garrido, J., Rodríguez-Bertos, A., Domínguez, M., Juste, R., Domínguez, L., Gortázar, C., & Risalde, M. A. (2025). Protective effect of heat-inactivated Mycobacterium bovis applied intramuscularly is associated with enhanced lung immune response in caprine tuberculosis. Veterinary Research, 56(1), 209. https://doi.org/10.1186/s13567-025-01634-50928-424910.1186/s13567-025-01634-5https://hdl.handle.net/20.500.14352/126515Author Contributions All authors contributed important elements to the work presented in this paper. Concept formulation: IAR, JB, MD, LD, CG, and MAR. Methodology: IAR, LMF, AR, JB, IAS, IM, ARB, and JG. Data analysis: IAR, LMF, RJ, and MAR. Writing the original draft: IAR, LMF, and MAR. Editing: IAG and MAR. Funding acquisition: MAR and CG. All authors read and approved the final manuscriptCaprine 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 functionsengAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/journal article1297-9716https://doi.org/10.1186/s13567-025-01634-541189022open access636.09Animal tuberculosisCapra hircusHIMBPulmonary immune responseVaccineVeterinaria3109 Ciencias Veterinarias