This proposal is concerned with the in vitro metabolism, efferent and afferent function of mouse and human mononuclear phagocytes in experimental leprosy. Our studies will explore further the already demonstrated defect in the response to lymphokines of lepromatous macrophages from M. leprae-infected nu/nu mouse footpads and the already demonstrated defect in the response to lymphokines of mouse macrophages burdened with viable M. leprae or M. leprae constituents. We will extend these studies to include human monocyte-derived macrophages. These studies will include exploration of efferent function, afferent function and mechanisms underlying the defect, including further investigation of the role of arachidonic acid metabolites in down regulation of macrophage efferent and afferent function. Using procedures developed in our lab, we will explore further the in vitro microbicidal capacity of human (leprosy patients and normals) monocytes and activated monocyte-derived macrophages and mouse peritoneal macrophages on the leprosy bacillus itself. Finally, we will explore the in vivo recruitment and turnover of bone marrow-derived macrophages in the lesions of M. leprae- infected nu/nu mice, an animal model for lepromatous leprosy and correlate our findings with changes in lepromatous macrophage function observed during long term chemotherapy with rifampin and immunotherapy with interferon gamma.
Showing the most recent 10 out of 18 publications
