The study of Mycobacterium leprae infection in interferon-gamma gene--disrupted mice as a model to explore the immunopathologic spectrum of leprosy.
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.
Adams
Linda B
LB
National Hansen's Disease Programs, Laboratory Research Branch, Louisiana State University, Baton Rouge, Louisiana 70803, USA.
Scollard
David M
DM
Ray
Nashone A
NA
Cooper
Andrea M
AM
Frank
Anthony A
AA
Orme
Ian M
IM
Krahenbuhl
James L
JL
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005528:Foot / Q000382:microbiology / Q000473:pathology; D017353:Gene Deletion; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000235:genetics*; D007918:Leprosy / Q000276:immunology* / Q000382:microbiology / Q000503:physiopathology*; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D017737:Macrophages, Peritoneal / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009166:Mycobacterium leprae / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity*
D016207:Cytokines; D007371:Interferon-gamma