[Frontiers in Bioscience 3, d525-531, June 8, 1998] |
MECHANISM OF MYCOBACTERIUM AVIUM COMPLEX PATHOGENESIS
Department of Medicine, University of Illinois at Chicago, Rm 864, M/C 735, 808 S.Wood st., Chicago, IL 60612
Received 5/4/98 Accepted 5/8/98
Intestinal or lung colonization precedes the development of MAC disease in AIDS patients. Even though normal healthy individuals are exposed to MAC, they rarely develop disease because the microorganisms fail to colonize, probably due to lack or inaccessibility of MAC binding receptors on the epithelial cells. It is quite possible that HIV infection directly or indirectly upregulates the expression of the surface receptors of intestinal and lung epithelial cells predisposing to MAC colonization. Structural changes in the microorganisms as a result of variation in colony morphology contributes to the virulence of the organisms significantly. Interaction of the microorganisms with different cells through specific receptors results in the release of cytokines and other mediators. The cascade of events (figure 1) initiated following the interaction of the microorganisms with epithelial and mononuclear phagocytic cells results in generation of macrophages endowed with increased killing of the invading microorganisms. These events direct and orchestrate the process of protection or pathogenesis. Macrophages are believed to kill the microorganisms through release of reactive oxygen radicals (02-,0H, H202 and NO) as well as lysosomal enzymes. A delicate balance in the levels of cytokines and oxygen metabolites released during infection needs to be maintained in order to generate effective immunity. Identification and characterization of MAC adhesins and host cell receptors involved in generation of the protective response and understanding the mechanisms involved in the interaction of the MAC with the host will help in devising protective measures against MAC induced disease.
Figure 1. Cascade of events following the interaction of Mycobacterium avium with host cells.