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item McGarvey, Jeffery - Jeff

Submitted to: Clinical and Experimental Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/29/2004
Publication Date: 6/1/2004
Citation: Mcgarvey, J.A., Bermudez, L.E. 2004. Differential gene expression in mononuclear phagocytes infected with pathogenic and non-pathogenic mycobacteria. 136(6:490-500.

Interpretive Summary: My mycobacteria are a group of bacteria that can cause disease in agriculturally important animals such as cows (Johne's Disease) and in Humans (tuberculosis). It is not known what enables these bacteria to cause disease, but it is believed that the host's (cow or human) defense against these intruding bacteria is inadequate. We looked at the response of host cells after infection with these bacteria an found that several genes that are usually turned on when invading bacteria are present, were not turned on after infection with these mycobacteria. We also observed that some genes that were normally turned off when invading bacteria are present were turned on. From these clues we conclude that the host cells play an important role in the interaction of the mycobacteria. This research furthers our understanding of the host factors involved in disease and may allow for the development of better protection strategies.

Technical Abstract: The pathogenic mycobacteria are in insidious group of bacterial pathogens that cause the deaths of millions of people every year. One of the reasons these pathogens are so successful is that they are able to invade and replicate within host macrophages, one of the first lines of defense against intruding pathogens. In contrast, nonpathogenic mycobacteria, such as (M. smegmatis) are rapidly killed by macrophages. In order to better understand the series of events that allow pathogenic mycobacteria to survive and replicate within macrophages, while the nonpathogenic mycobacteria are rapidly killed, we inoculated the human monocytic cell line U937 with pathogenic (M. tuberculosis and M. avium) and nonpathogenic (M.smegmatis) mycobacteria and monitored the expression of over 3,500 genes at 4, 12 and 24 h post inoculation using commercially available gene array system. We observed multiple differences in the gene expression patterns of macrophages infected with pathogenic and nonpathogenic mycobacteria including genes involved in cytokine, lymphokine and chemokine production, adhesion, apoptosis, signal transduction, transcription, protein cleavage, action polymerization and growth. We also observed differences in gene expression profiles in macrophages infected with M. tuberculosis or M. avium, indicating that there are different pathogenic mycobacterial species. These results increase the understanding of the mechanisms used by pathogenic mycobacteria to cause disease, the host response to these organisms, and provide new insights for anti-mycobacterial intervention strategies.