| Abstract: |
Tumour necrosis factor-α (TNF) plays a central role in the recruitment and activation of mononuclear cells in mycobacterial infection. In the absence of type 1 TNF receptor, Mycobacterium bovis Bacillus Calmette-Guerin (BCG) infection of mice is not contained, leading to fatal disease. Because type 1 TNF receptor binds both TNF and lymphotoxin-α, we used TNF-deficient mice to determine the specific role of TNF in the host resistance to BCG infection. The bacterial burden of the lungs of TNF-deficient mice was substantially increased and the mice succumbed to pneumonia between 8 and 12 weeks with a defective granuloma response. Atypical granulomas developed by 4 weeks expressing low levels of MHC class II, intracellular adhesion molecule (ICAM-1), CD11b and CD11c. Macrophages showed little signs of activation and had low levels of acid phosphatase activity and inducible nitric oxide synthase (INOS) expression. Despite the defective cellular recruitment, the chemokines, monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1 (MIP-1α), were increased in broncho-alveolar lavage fluid of TNF-deficient mice. The defective host response was corrected by the transplantation of normal bone marrow cells into irradiated TNF-deficient mice. These results demonstrate that TNF derived from hemopoietic cells rather than from mesenchymal origin are essential for a normal host response to BCG infection. Furthermore, TNF dependent expression of adhesion molecules may be essential for the recruitment of mononuclear cells for the formation of bactericidal BCG granulomas. |
| Keywords: |
controlled study; protein expression; nonhuman; antigen expression; mouse; animals; mice; mice, knockout; animal tissue; animal experiment; animal model; mice, inbred c57bl; pneumonia; immune response; chemokine; mononuclear cell; tumor necrosis factor-alpha; cd11b antigen; major histocompatibility antigen class 2; mycobacterium bovis; lung; antigens, cd; host resistance; macrophage; histocompatibility antigens class ii; bone marrow transplantation; cell activation; intercellular adhesion molecule 1; monocyte chemotactic protein 1; mycobacteriosis; tuberculosis; nitric oxide synthase; granuloma; tumor necrosis factor; intercellular adhesion molecule-1; receptors, tumor necrosis factor; lung lavage; acid phosphatase; glycoprotein p 15095; immunity, natural; receptors, tumor necrosis factor, type i; female; priority journal; article; macrophage-1 antigen; lung burden; integrin alphaxbeta2; macrophage inflammatory protein 1
|
