title: Tumor necrosis factor receptor 2 plays a minor role for mycobacterial immunity.
abstract: Tumor necrosis factor (TNF) signalling via the TNF receptor 1 (TNF-R1) is required for host resistance to mycobacterial infection. The role of TNF-R2 in anti-mycobacterial immunity is not known. Therefore, we compared TNF-R1 and TNF-R2 knockout (KO) mice infected with Mycobacterium bovis BCG (10(7) CFU, i.v.). While the bacterial burden of TNF-R1-deficient mice was significantly increased and the mice succumbed to infection between 4 and 5 weeks, TNF-R2 KO mice were less sensitive, and only 3 of 10 mice died within 12 weeks. Wild-type (WT) mice were resistant to BCG infection. The inability to clear the infection of TNF-R1 KO mice was associated with a reduced delayed-type hypersensitivity (DTH) response to purified protein derivative and severe impairment in forming granulomas with reduced macrophage recruitment and activation, and diminished expression of adhesion molecules. By contrast, TNF-R2 KO mice developed normal DTH response and mature mycobactericidal granulomas as the WT mice. Therefore, anti-mycobacterial immunity is largely dependent on TNF signalling via the TNF-R1, while activation of TNF-R2 plays a minor role.
authors.affiliation: Department of Immunology, University of 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: K
authors.initials: K
authors.lastname: Chetty
authors.forename: B
authors.initials: B
authors.lastname: Ryffel
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D002417:Cattle; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D015769:Granuloma, Respiratory Tract / Q000382:microbiology / Q000473:pathology; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000382:microbiology; D007111:Immunity, Cellular; D007113:Immunity, Innate / Q000235:genetics; D008099:Liver / Q000382:microbiology / Q000473:pathology; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008264:Macrophages / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009163:Mycobacterium bovis / Q000276:immunology*; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D015996:Survival Rate; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology / Q000401:mortality
chemical_list: D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II