title: Fatal Mycobacterium bovis BCG infection in TNF-LT-alpha-deficient mice.
abstract: Neutralization of TNF or disruption of TNF-R1 leads to fatal Mycobacterium bovis BCG infection. Here we used TNF-LT-alpha-deficient mice to test whether a complete disruption of TNF and LT-alpha reduces further host resistance to BCG infection. The bacterial burden especially in the lungs of TNF-LT-alpha-deficient mice was significantly increased and the mice succumbed to infection between 8 and 10 weeks. In the absence of TNF-LT-alpha the granulomatous response was severely impaired and delayed. The cells in the granulomas of TNF-LT-alpha-deficient mice expressed low levels of MHC class II and ICAM-1. They contained a few T cells and F4/80-positive macrophages expressing little iNOS and acid phosphatase activity. By contrast, the lethal action of endotoxin was dramatically reduced in BCG-infected TNF-LT-alpha-deficient mice. In summary, in the absence of TNF-LT-alpha the recruitment and activation of mononuclear cells in response to BCG infection were significantly delayed and reduced resulting in immature granulomas allowing uncontrolled fatal infection.
authors.affiliation: Department of Immunology, University of Cape Town, Cape Town, South Africa.
authors.forename: M
authors.initials: M
authors.lastname: Jacobs
authors.forename: N
authors.initials: N
authors.lastname: Brown
authors.forename: N
authors.initials: N
authors.lastname: Allie
authors.forename: B
authors.initials: B
authors.lastname: Ryffel
mesh_terms: D000818:Animals; D004731:Endotoxins / Q000633:toxicity; D006099:Granuloma / Q000209:etiology; D006968:Hypersensitivity, Delayed / Q000382:microbiology; D008233:Lymphotoxin-alpha / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009163:Mycobacterium bovis / Q000254:growth & development / Q000276:immunology; D014375:Tuberculoma / Q000209:etiology; D014376:Tuberculosis / Q000662:veterinary*; D014386:Tuberculosis, Hepatic / Q000209:etiology; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency
chemical_list: D004731:Endotoxins; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha