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Lipoarabinomannan, a possible virulence factor involved in persistence of Mycobacterium tuberculosis within
1Department of Medicine, University of Medicine and Dentistry of New Jersey, Newark 07103.
Abstract:
Mycobacterium tuberculosis and Mycobacterium leprae, the causative agents of tuberculosis and leprosy, respectively, produce large quantities of lipoarabinomannan (LAM), a highly immunogenic, cell wall-associated glycolipid. This molecule has been previously reported to be a potent inhibitor of gamma interferon-mediated activation of murine macrophages. Studies of the mechanism by which this mycobacterial glycolipid down-regulates macrophage effector functions provide evidence that LAM acts at several levels and that it can (i) scavenge potentially cytotoxic oxygen free radicals, (ii) inhibit protein kinase C activity, and (iii) block the transcriptional activation of gamma interferon-inducible genes in human macrophage-like cell lines. These results suggest that LAM can inhibit macrophage activation and triggering and cytocidal activity and that it may represent a chemically defined virulence factor contributing to the persistence of mycobacteria within mononuclear phagocytes.
Insights
Lipoarabinomannan (LAM) from Mycobacterium tuberculosis and leprae inhibits macrophage activation by scavenging free radicals, blocking protein kinase C, and preventing gene activation. This glycolipid may be a key virulence factor for mycobacterial persistence.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Mycobacterium tuberculosis and Mycobacterium leprae cause tuberculosis and leprosy.
- These bacteria produce lipoarabinomannan (LAM), a potent glycolipid.
- LAM is known to inhibit gamma interferon-mediated activation of macrophages.
Purpose of the Study:
- To investigate the mechanisms by which LAM down-regulates macrophage effector functions.
- To identify how LAM contributes to mycobacterial virulence and persistence.
Main Methods:
- Studied the effects of LAM on macrophage activation and function.
- Investigated LAM's impact on oxygen free radicals, protein kinase C activity, and gene transcription in macrophage-like cell lines.
Main Results:
- LAM scavenges cytotoxic oxygen free radicals.
- LAM inhibits protein kinase C activity.
- LAM blocks the transcriptional activation of gamma interferon-inducible genes in human macrophage-like cell lines.
Conclusions:
- LAM inhibits macrophage activation, triggering, and cytocidal activity.
- LAM is a chemically defined virulence factor.
- LAM likely contributes to the persistence of mycobacteria within mononuclear phagocytes.