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.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Unknown (R22)
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Bacteriology and Mycology Subcommittee 2 (BM)
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National Hansen's Disease Program
Baton Rouge
United States
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Adams, L B; Gillis, T P; Hwang, D H et al. (1997) Effects of essential fatty acid deficiency on prostaglandin E2 production and cell-mediated immunity in a mouse model of leprosy. Infect Immun 65:1152-7
Adams, L B; Fukutomi, Y; Krahenbuhl, J L (1993) Regulation of murine macrophage effector functions by lipoarabinomannan from mycobacterial strains with different degrees of virulence. Infect Immun 61:4173-81
Adams, L B; Franzblau, S G; Vavrin, Z et al. (1991) L-arginine-dependent macrophage effector functions inhibit metabolic activity of Mycobacterium leprae. J Immunol 147:1642-6
Ramasesh, N; Adams, L B; Franzblau, S G et al. (1991) Effects of activated macrophages on Mycobacterium leprae. Infect Immun 59:2864-9
Sibley, L D; Adams, L B; Fukutomi, Y et al. (1991) Tumor necrosis factor-alpha triggers antitoxoplasmal activity of IFN-gamma primed macrophages. J Immunol 147:2340-5
Adams, L B; Hibbs Jr, J B; Taintor, R R et al. (1990) Microbiostatic effect of murine-activated macrophages for Toxoplasma gondii. Role for synthesis of inorganic nitrogen oxides from L-arginine. J Immunol 144:2725-9
Sibley, L D; Adams, L B; Krahenbuhl, J L (1990) Inhibition of interferon-gamma-mediated activation in mouse macrophages treated with lipoarabinomannan. Clin Exp Immunol 80:141-8
Ramasesh, N; Krahenbuhl, J L; Hastings, R C (1989) In vitro effects of antimicrobial agents on Mycobacterium leprae in mouse peritoneal macrophages. Antimicrob Agents Chemother 33:657-62
Hastings, R C; Gillis, T P; Krahenbuhl, J L et al. (1988) Leprosy. Clin Microbiol Rev 1:330-48
Sibley, L D; Krahenbuhl, J L (1988) Induction of unresponsiveness to gamma interferon in macrophages infected with Mycobacterium leprae. Infect Immun 56:1912-9

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