The bovine is a robust animal model for preclinical safety and efficient evaluation of TB candidate vaccines targeting human population. Therefore, biomarkers can also be used to anticipate the outcome of vaccine TB-protection assays in bovine models of infection. In this study, we aimed to evaluate the gene expression profile of bovine peripheral blood mononuclear cells from cattle infected with M. bovis upon specific antigen stimulation. We found that more than 5,930 genes changed their level of expression upon infection of cattle with M. bovis. Further evaluation of RNA expression levels in PBMCs from cattle experimentally infected with M. bovis confirmed the microarray results for a subset of genes. In the current study, we compared the gene expression profile induced in PBMCs from M. bovis-infected cattle with that of healthy cattle. PBMCs represent an accessible tissue for the development of improved diagnostics. Moreover, previous studies have shown that the immune responses generated in the peripheral blood of cattle with tuberculosis reflect those elicited at the site of the disease. This comparative transcriptional profile identified gene expression pathways involved in immune and inflammatory responses, apoptosis, endocytosis and cellular trafficking as highly downregulated in M. bovis-infected animals. Remarkably, the expression of several matrix metallopeptidases was significantly downregulated in infected animals. Only a few genes were significantly upregulated in infected animals and most of them encoded immune response-related proteins, such as IFNc, interleukines, etc. Consistent with the findings of this study, it has been previously reported, in several studies, that the immunospecific gene expression undergoes shutoff in M. bovis-infected cattle. Meade and coworkers have shown that the expression of several genes involved in the innate immune response was suppressed in M. bovis-infected cattle. In addition, two consecutive studies of the same research group have WY 14643 moa reported that the balance in the transcriptional changes induced by M. bovis in different cell blood populations is suppression of gene expression. To determine the main biological processes associated with the differentially expressed genes, we clustered these genes in cellular pathways. In this analysis, we included all differentially-expressed genes that passed the statistical test without considering the fold changes. We observed statistically significant enrichment of induced genes in several pathways, but except for those encoding proteins involved in the T cell receptor signaling pathway, most of them were related to unspecific biological functions. In contrast, the repressed genes were mainly categorized in cellular trafficking pathways, such as endocytosis, phagosome, lysosome, MAP kinase signaling and regulation of the cytoskeleton, all functions associated with tuberculosis infections. As mentioned above, the expression of four metallopeptidases was dowregulated in PBMCs of infected animals. However, further studies have demonstrated that MMPs can modify many non-matrix substrates, such as cytokines and chemokines. Chemokines play a central role in leukocyte recruitment to the site of infection, influencing the result of the inflammatory response. Proteolysis of chemokines by MMPs can either reduce or potentiate their activities. It has been reported that MMP3 inactivates several chemokines, while MMP9 increases the potency of at least two chemokines and inactivates several others. The role of MMP9 in tuberculosis infection has been extensively studied. MMP9 is induced in cultured M. tuberculosis-infected monocytes and in epithelial cells, and it promotes granuloma formation.