TY - JOUR KW - Animals KW - CD4-Positive T-Lymphocytes KW - CD8-Positive T-Lymphocytes KW - Cytokines KW - Disease Models, Animal KW - Flow Cytometry KW - Foot KW - Gene Deletion KW - Humans KW - Immunohistochemistry KW - Interferon-gamma KW - leprosy KW - Lymph Nodes KW - Lymphocyte Activation KW - Macrophages, Peritoneal KW - Mice KW - Mice, Inbred BALB C KW - Mice, Knockout KW - Mycobacterium leprae AU - Adams LW AU - Scollard D AU - Ray NA AU - Cooper AM AU - Frank A AU - Orme I AU - Krahenbuhl JL AB -

Mycobacterium leprae infection was evaluated in interferon-gamma knockout (GKO) mice. At 4 months, growth of the bacilli in the footpads of GKO mice plateaued a log(10) higher than that in control mice. Control mice exhibited mild lymphocytic and histiocytic infiltrates, whereas GKO mice developed large, unorganized infiltrates of epithelioid macrophages and scattered CD4 and CD8 T cells. Flow cytometric analysis of popliteal lymph node cells demonstrated similar profiles of T cells; however, GKO cells exhibited an elevated proliferative response to M. leprae antigen. Expression of inducible nitric oxide synthase mRNA was decreased in GKO mice, whereas macrophage inflammatory protein-1alpha and interleukin-4 and -10 mRNA expression were augmented. Control and GKO activated macrophages inhibited bacterial metabolism and produced nitrite. Thus, although deficient in an important Th1 cytokine, GKO mice possess compensatory mechanisms to control M. leprae growth and feature elements resembling mid-borderline leprosy in humans.

BT - The Journal of infectious diseases C1 - http://www.ncbi.nlm.nih.gov/pubmed/11865434?dopt=Abstract DA - 2002 Feb 15 DO - 10.1086/338002 J2 - J. Infect. Dis. LA - eng N2 -

Mycobacterium leprae infection was evaluated in interferon-gamma knockout (GKO) mice. At 4 months, growth of the bacilli in the footpads of GKO mice plateaued a log(10) higher than that in control mice. Control mice exhibited mild lymphocytic and histiocytic infiltrates, whereas GKO mice developed large, unorganized infiltrates of epithelioid macrophages and scattered CD4 and CD8 T cells. Flow cytometric analysis of popliteal lymph node cells demonstrated similar profiles of T cells; however, GKO cells exhibited an elevated proliferative response to M. leprae antigen. Expression of inducible nitric oxide synthase mRNA was decreased in GKO mice, whereas macrophage inflammatory protein-1alpha and interleukin-4 and -10 mRNA expression were augmented. Control and GKO activated macrophages inhibited bacterial metabolism and produced nitrite. Thus, although deficient in an important Th1 cytokine, GKO mice possess compensatory mechanisms to control M. leprae growth and feature elements resembling mid-borderline leprosy in humans.

PY - 2002 SP - S1 EP - 8 T2 - The Journal of infectious diseases TI - The study of Mycobacterium leprae infection in interferon-gamma gene--disrupted mice as a model to explore the immunopathologic spectrum of leprosy. VL - 185 Suppl 1 SN - 0022-1899 ER -