Resistance mechanisms in murine experimental histoplasmosis.
The study by use of immunocytochemical methods shows that the spleen of mouse infected intravenously by Histoplasma capsulatum is heavily infiltrated by macrophages. The CD4+ and CD8+ T cells are diffused and sparsely distributed throughout the spleen. It appears that experimental histoplasmosis in animals presents as a disease of the mononuclear phagocyte systems. Macrophages are important cells in controlling replication of intracellular H. capsulatum. Factors that affect the infiltration and activation of macrophages are, thus, important in host defense against histoplasmosis. Depletions of endogenous TNF-alpha in animals infected with sublethal dose of H. capsulatum results in death of these animals. The fungus burden in these animals is high and macrophages are not capable of restricting proliferations of the fungus. However, the role of TNF-alpha in histoplasmosis is not a direct activation of macrophages and is still yet to be defined. IFN-gamma has been shown to fully activate mouse peritoneal macrophages and partially activate splenic macrophages for anti-histoplasma activity. The importance of IFN-gamma in host defense against histoplasmosis is studied by use of resistant A/J and susceptible C57BL/6 mouse strains. There is a good correlation of early production of IFN-gamma by spleen cells of infected mice with the ability of the animals to clear the infection. Spleen cells of resistant A/J mice are more efficient than susceptible C57BL/6 mice in production of IFN-gamma. Recombinant inbred progeny of A/J and C57BL/6 mice are used to locate the genes that control resistance to histoplasmosis. Preliminary studies show that the resistance phenotype is controlled not by a single gene but by multiple genes.
Wu-Hsieh
B A
BA
Department of Microbiology and Immunology, School of Medicine, University of California at Los Angeles 90024-1747.
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D006660:Histoplasmosis / Q000276:immunology*; D007111:Immunity, Cellular; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000502:physiology; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics / Q000276:immunology; D012008:Recurrence; D013154:Spleen / Q000382:microbiology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma