Another possibility is that intracellular PRRs mediate autophagy in infected macrophages, which is increasingly regarded as a key antimycobacterial host defence mechanism. Autophagy is a complex cellular process in which host cell cytosolic components, such as damaged or surplus organelles, are engulfed in doublemembrane vesicles called autophagosomes and fused with late endosomes or lysosomes to degrade their contents. However, further work is required to investigate a role for RLR- and TLR3mediated autophagy in response to mycobacterial infection. Macrophage apoptosis is increasingly regarded as a host innate Shikonofuran-A immune mechanism in controlling mycobacterial infection by containing and limiting mycobacterial growth. Recently, microarray-based studies of mycobacterial infection of bovine macrophages in vitro revealed over-representation of genes associated with apoptosis among the list of differentially expressed genes. The detection of apoptotic signatures of gene expression here supports this earlier work and indicates that apoptosis is an early response of host MDM to M. bovis infection. Although analysis of the differentially expressed genes following M. bovis-challenge largely supports induction of a pro-apoptotic response in these cells, presumably to eliminate the intracellular pathogen, the increased relative expression of several antiapoptotic genes suggests that this process is highly regulated. Rilmenidine Phosphate Anti-apoptotic signals may represent a host mechanism to limit the amount of cell death following infection and may also enable improved antigen-presentation by infected macrophages to T cells, resulting in either elimination of the pathogen or enhanced granuloma formation. It is also possible that the antiapoptotic signals detected here represent transcriptional signatures of ����bystander���� apoptosis, whereby uninfected macrophages undergo apoptosis following contact with mycobacteria-infected macrophages. Alternatively, the induction of anti-apoptotic genes may signify an immuno-subversion mechanism used by the pathogen that postpones apoptosis and enables survival and replication within the macrophage. Indeed, recent studies have shown that virulent M. tuberculosis can subvert host apoptotic pathways by interfering with the production of key host signalling molecules, resulting in the arrest of apoptosis and induction of necrosis, thereby offering an exit route from the macrophage. Therefore, induction of anti-apoptotic genes as identified by the current study may provide another strategy used by the pathogen for the evasion of the host immune system. The innate immune response to mycobacterial pathogens is largely mediated by immuno-regulatory cytokines and chemokines secreted by various immune cells that regulate the recruitment and expansion of immune cell populations, such as monocytes, neutrophils, T cells and other effector cells from the blood to the site of infection. Macrophage production of cytokines and chemokines in response to mycobacterial infection can be induced through a wide range of PRR-mediated pathways, and their secretion primes the adaptive immune response, which is pivotal in determining pathogenesis. In the current study, several inflammatory chemokine and cytokine genes were shown to display large increases in relative expression following M. bovis-challenge across all of the time points analysed, with systems analysis showing that many of the top ranking GO categories were enriched for large numbers of these genes.