Immunoactive Proteins of Mycobacterium bovis: From Molecular Mechanisms to Biomarkers and Vaccines

Abstract

Background and Aim. Mycobacterium bovis is a zoonotic member of the Mycobacterium tuberculosis complex and the causative agent of bovine tuberculosis, posing significant challenges to veterinary health, wildlife management and public health. Despite high genomic similarity to M. tuberculosis, M. bovis exhibits distinct host–pathogen interaction strategies that influence immune recognition, persistence and disease progression. This review aims to systematize and critically synthesize current knowledge on immunoactive proteins of M. bovis and to elucidate their roles in modulation of innate and adaptive immune responses, with particular emphasis on mechanisms of immune evasion, diagnostic relevance and vaccine potential.

Materials and Methods. This narrative review synthesizes peer-reviewed literature retrieved from international scientific databases. Studies addressing molecular genetics, proteomics, tran-scriptomics, host immune signaling pathways, and experimental infection models of M. bovis were critically evaluated. Special attention was given to proteins involved in phagocytosis, autophagy, Toll-like receptor (TLR) signaling and cytokine regulation, as well as to comparative studies with M. tuberculosis.

Results. The analysis indicates that M. bovis actively modulates macrophage defense mechanisms through multiple molecular axes, including inhibition of phagosome–lysosome fusion, selective activation of PINK1 Parkin-dependent mitophagy and suppression of xenophagy. Key immunoactive proteins, such as ESAT-6, CFP-10, MPB70/80/83, PE/PPE proteins and lipoproteins, play central roles in shaping both inflammatory and regulatory immune responses. Activation of cytosolic DNA sensors, particularly Interferon-Inducible Protein 204 (IFI204), and downstream IFN-β signaling is more pronounced in M. bovis infection and contributes to species-specific immune responses. Differential expression and secretion of these proteins underpin their value as diagnostic biomarkers and potential vaccine antigens.

Conclusion. Immunoactive proteins of M. bovis form a complex molecular network that enables immune modulation, intracellular persistence and host adaptation. Their functional significance extends beyond virulence, positioning them as promising targets for Differentiating Infected from Vaccinated Animals (DIVA)-compatible diagnostics and second-generation vaccines. An integrated understanding of these mechanisms is essential for improving control strategies for bovine tubercu-losis and reducing the risk of zoonotic transmission.