Many of the upregulated inflammatory genes detected here have been shown to play an important role in the immune response to mycobacterial infection and several of these direct the transition from innate to adaptive Nimorazole immunity during infection. Indeed, the GO categories identified via systems analysis of the differentially expressed genes here suggest that the expression of macrophage genes involved in the communication between innate and adaptive immune cell types is a key biological process that occurs within the first 24 hours of M. bovis challenge in vitro. For example, TNF-a is a key pleiotropic cytokine produced by macrophages that plays an important role in granuloma formation and maintenance by inducing IFN-c release from T cells, which in turn, activates anti-mycobacterial function in infected macrophages. IL12 encodes a proinflammatory cytokine produced by macrophages that activates NK cells and T cells to produce IFN-c and promote the adaptive immune response to mycobacterial infection. IL-1b is a proinflammatory cytokine secreted largely by innate immune cells in response to mycobacterial infection and studies have shown that IL-1b is produced in excess at the site of infection, suggesting that it plays an important role in granuloma formation and maintenance. Genes encoding b-chemokines participate in early immuno-protection against mycobacterial pathogens following infection. IL-6, a pleiotropic inflammatory cytokine expressed by a wide range of immune cells including macrophages in response to mycobacterial infection, has been proposed to play an important role in protection against tuberculosis. IL6 displayed large fold-upregulation at all three time points analysed in the M. bovischallenged MDM, while the gene encoding the IL-6 receptor displayed Clopidol downregulation expression in the M. bovischallenged MDM at 2 hours and 24 hours and was not differentially expressed at the 6 hour time point. This suggests that endogenous IL-6 production by macrophages acts in an endocrine manner, presumably by initiating immune responses in other innate or adaptive immune cells. Indeed, IL-6 has been proposed as a key regulator of the immunological switch between innate and adaptive immune processes. Despite the role of chemokines and cytokines in directing the host immune response to control mycobacterial infection, there is evidence to suggest that their function can be used by mycobacterial pathogens to enable persistence within the host. For example, non-regulated production of TNF-a in lung tissue can result in immunopathology, including destructive inflammation and necrosis, allowing dissemination of the pathogen from infected cells. Furthermore, studies have shown that IL-6 can inhibit T cell responses following infection of macrophages with M. bovis-BCG and M. avium subspecies paratuberculosis, while other investigations have reported that M. tuberculosisinduced IL-6 production inhibits the anti-microbial activity of macrophages in response to IFN-c. IL10, which encodes an anti-inflammatory cytokine that limits local cytokine-induced tissue damage and systemic inflammatory responses during infection, was upregulated at 2 hours and 24 hours postchallenge. Interestingly, upregulation of IL10 resulting in the subsequent suppression of host innate immune responses to infection has been proposed as a mechanism which enables enhanced mycobacterial intracellular proliferation.