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

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 wheth er a complete disruption of TNF and LT-alpha reduces further host resistanc e 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 granul omatous response was severely impaired and delayed. The cells in the granul omas of TNF-LT-alpha-deficient mice expressed low levels of MHC class II an d ICAM-1. They contained a few T cells and F4/80-positive macrophages expre ssing little iNOS and acid phosphatase activity. By contrast, the lethal ac tion of endotoxin was dramatically reduced in BCG-infected TNF-LT-alpha-def icient mice. In summary, in the absence of TNF-LT-alpha the recruitment and activation of mononuclear cells in response to BCG infection were signific antly delayed and reduced resulting in immature granulomas allowing uncontr olled fatal infection. (C) 2000 Academic Press.