Tumor necrosis factor receptor 2 plays a minor role for mycobacterial immunity

Tumor necrosis factor (TNF) signalling via the TNF receptor 1 (TNF-R1) is r equired for host resistance to mycobacterial infection. The role of TNF-R2 in anti-mycobacterial immunity is not known. Therefore, we compa red TNF-R1 and TNF-R2 knockout (KO) mice infected with Mycobacterium bovis BCG (10(7) CFU, i.v.). While the bacterial burden of TN F-R l-deficient mice was sign ificantly increased and the mice succumbed to infection between 4 and 5 wee ks, TNF-R2 KO mice were less sensitive, and only 3 of 10 mice died within 1 2 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 del ayed-type hypersensitivity (DTH) response to purified protein derivative an d severe impairment in forming granulomas with reduced macrophage recruitme nt and activation, and diminished expression of adhesion molecules. By cont rast, TNF-R2 KO mice developed normal DTH response and mature mycobacterici dal granulomas as the WT mice. Therefore, anti-mycobacterial immunity is la rgely dependent on TNF signalling via the TNF-R1, while activation of TNF-R 2 plays a minor role. Copyright (C) 2000 S. Karger AG, Basel.