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Bovine tuberculosis is an important animal and zoonotic disease caused by  Mycobacterium bovis . The innate immune response is the first line of defense against pathogens and is also crucial for the development of an efficient adaptive immune response. In this study we used an  in vitro  co-culture model of antigen presenting cells (APC) and autologous lymphocytes derived from peripheral blood mononuclear cells to identify the cell populations and immune mediators that participate in the development of an efficient innate response capable of controlling the intracellular replication of  M. bovis . After  M. bovis  infection, bovine immune cell cultures displayed upregulated levels of iNOS, IL-22 and IFN-γ and the induction of the innate immune response was dependent on the presence of differentiated APC. Among the analyzed  M. bovis  isolates, only a live virulent  M. bovis  isolate induced an efficient innate immune response, which was increased upon stimulation of cell co-cultures with the  M. bovis  culture supernatant. Moreover, we demonstrated that an allelic variation of the early secreted protein ESAT-6 (ESAT6 T63A) expressed in the virulent strain is involved in this increased innate immune response. These results highlight the relevance of the compounds secreted by live  M. bovis  as well as the variability among the assessed  M. bovis  strains to induce an efficient innate immune response.

Identifying Bacterial and Host Factors Involved in the Interaction of Mycobacterium bovis with the Bovine Innate Immune Cells