Fatal Mycobacterium bovis BCG Infection in TNF-LT-α-Deficient Mice |
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Authors: | Muazzam Jacobs Najmeeyah Brown Nasiema Allie Bernhard Ryffel |
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Institution: | Department of Immunology, University of Cape Town, Cape Town, South Africa |
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Abstract: | Neutralization of TNF or disruption of TNF-R1 leads to fatal Mycobacterium bovis BCG infection. Here we used TNF-LT-α-deficient mice to test whether a complete disruption of TNF and LT-α reduces further host resistance to BCG infection. The bacterial burden especially in the lungs of TNF-LT-α-deficient mice was significantly increased and the mice succumbed to infection between 8 and 10 weeks. In the absence of TNF-LT-α the granulomatous response was severely impaired and delayed. The cells in the granulomas of TNF-LT-α-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-α-deficient mice. In summary, in the absence of TNF-LT-α 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. |
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Keywords: | BCG TNF LT-α ICAM-1 LPS |
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