Leprosy is one of the major diseases of the world. It afflicts approximately 12-15 million people worldwide, and because of its chronicity, it has tremendous social and economic consequences in addition to health consequences. In the U.S.A., approximately 3000 persons have leprosy, and the number of newly diagnosed cases has been increasing yearly. As with most diseases caused by intracellular pathogens, prevention and therapy of leprosy is unsatisfactory in part because more needs to be learned about the biology of the interaction between the host cell and pathogen. Specifically, more needs to be learned about phagocytosis of these organisms and their intracellular biology in human mononuclear phagocytes. The proposed studies should lay the groundwork for formulating new strategies for the prevention and treatment of leprosy.
Specific aims are to: a) Determine the role of complement in binding and uptake of M. leprae by monocytes: b) Determine the role of monocyte CR1 and CR3 receptors in phagocytosis of M. leprae; c) Determine the mechanism of phagocytosis (coiling or conventional) of M. leprae; d) Determine the morphology of the phagosomes formed after phagocytosis of M. leprae and determine the evolution of the phagosome in monocytes; e) Determine if M. leprae inhibits fusion of the phagosome with monocyte primary and secondary lysosomes; f) Determine the influence of gamma interferon activation of monocytes on phagocytosis of M. leprae, phagosome formation, and phagosome-lysosome fusion; g) Determine the influence of antibody against M. leprae on phagocytosis, phagosome formation, and phagosome-lysosome fusion.
