Mycobacterium avium subspecies paratuberculosis (MAP) is a significant concern both to the American Dairy industry and in regards to human health. MAP causes a chronic inflammatory disease in ruminants known as Johne's disease. Johne's disease affects over 68% of American dairy farms and causes over $1.5 billion in losses each year to the dairy industry. Pasteurization does not destroy all MAP bacteria. Therefore, viable MAP has been detected in commercially available milk, meat, and cheese. Further troubling, MAP has been linked to the human inflammatory condition known as Crohn's disease. The root cause of the chronic inflammation in these diseases is the ability of MAP to prevent macrophage phagosome maturation and intracellular survival. Our group, the molecular pathogenesis laboratory, is interested in the complex interactions between the infecting MAP bacteria and the host macrophage. Previously, we found that MAP altered the transcriptome of infected cultures. Based on these results, my work focused on studying the common pathways altered in MAP-infected macrophages. My initial work used 10 different MAP strains isolated from four different species. By using such a large variety of MAP strains, we established the transcriptome elements that are commonly altered in MAP infection. Through this work, we found several host pathways that are altered in MAP infection. As part of this work, we reannotated the BOTL5 microarray. To help other researchers, we provided the methodology and scripts necessary for easy reannotation of other microarrays. Among the pathways altered in MAP-infected macrophages, we found apoptosis to be regulated. continuing our studies in this area, we found significant differences between MAP-infected macrophages and uninfected culture mates. our studies also indicated that regulation of caspase activation and transcription may explain the different levels of apoptosis in MAP-infected and control cells. The net result of our work was a deeper understanding of the complex interaction between the bovine macrophages and infecting MAP with a particular focus on MAP-mediated regulation of host cell apoptosis.
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