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Immune System Evasion Generally, M. leprae manages to avoid the immune system through its unique lifecycle: by replicating exclusively inside of macrophages and Schwann cells, most phagocytes and antigen-presenting cells do not encounter the pathogen. This lack of meeting causes a paucity of immune response – hence, M. leprae stays mainly silent. (3 - Janeway et al, 2005 Figure1-26)
Apoptosis Prevention: A good summary of this trend can be found here. Like M. tuberculosis (which is a mycobacterium similar to M. leprae that causes tuberculosis), M. leprae is also able to prevent host macrophage apoptosis in vitro (4). While this may not be the case in vivo, it is an interesting point that the bacterium is able at least in vitro to affect the sensitivity of the host cell to apoptosis. The mycobacteria find a way to increase expression of Fas-ligand and decrease expression of the Fas receptor on the surface of the macrophages (4). This allows the macrophage to protect itself against killing by CD8+ T-cells (3). Fas ligand is usually only expressed by the CD8+ cell itself and recognizes the Fas receptor on infected cells (3). Therefore, the host macrophages’ increase of Fas-ligand expression serves to hide it from recognition by the CD8+ T-cell. By this mechanism, M. leprae may (in vivo) be able to evade immune system recognition by CD8+ T-cells, thereby avoiding the results of a Th1 predominant response (2).
Induction of anergy:
Sources: 2. Hasan, Z., Ashraf, M., Tayyebi, A., Hussain, R. 2006. M. leprae inhibits apoptosis in THP-1 cells by downregulation of Bad and Bak and upregulation of Mcl-1 gene expression. BMC Micro. 6:78. 3. Janeway, C., Travers, P., Walport, M., Shlomchik M. Immuno Biology: the immune system in health and disease. 6th Ed. 2005. New York: Garland Science Publishing. 4. Mustafa, T., Bjune, G., Jonsson, R., Hernandez Panno, R., Nilsen, R. 2001. Increased expression of Fas ligand in human tuberculosis and leprosy lesions: a potential novel mechanism of immune evasion in mycobacterial infection. Scand J Immunol. 54:630-639.
Copyright Alex Greer 2007 For questions/comments, please contact Immunology professor Dr. Sofia Sarafova at Davidson College. |