Fatal Mycobacterium bovis BCG infection in TNF-LT-alpha-deficient mice

Clin Immunol. 2000 Mar;94(3):192-9. doi: 10.1006/clim.2000.4835.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Endotoxins / toxicity
  • Granuloma / etiology
  • Hypersensitivity, Delayed / microbiology
  • Lymphotoxin-alpha / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Mycobacterium bovis* / growth & development
  • Mycobacterium bovis* / immunology
  • Tuberculoma / etiology
  • Tuberculosis / veterinary*
  • Tuberculosis, Hepatic / etiology
  • Tumor Necrosis Factor-alpha / deficiency


  • Endotoxins
  • Lymphotoxin-alpha
  • Tumor Necrosis Factor-alpha