Correction of defective host response to Mycobacterium bovis BCG infectionin TNF-deficient mice by bone marrow transplantation

Citation
M. Jacobs et al., Correction of defective host response to Mycobacterium bovis BCG infectionin TNF-deficient mice by bone marrow transplantation, LAB INV, 80(6), 2000, pp. 901-914
Citations number
39
Categorie Soggetti
Medical Research General Topics
Journal title
LABORATORY INVESTIGATION
ISSN journal
00236837 → ACNP
Volume
80
Issue
6
Year of publication
2000
Pages
901 - 914
Database
ISI
SICI code
0023-6837(200006)80:6<901:CODHRT>2.0.ZU;2-N
Abstract
Tumour necrosis factor-alpha (TNF) plays a central role in the recruitment and activation of mononuclear cells in mycobacterial infection. In the abse nce of type 1 TNF receptor, Mycobacterium bovis Bacillus Calmette-Guerin (B CG) infection of mice is not contained, leading to fatal disease. Because t ype 1 TNF receptor binds both TNF and lymphotoxin-alpha, we used TNF-defici ent mice to determine the specific role of TNF in the host resistance to BC G infection. The bacterial burden of the lungs of TNF-deficient mice was su bstantially increased and the mice succumbed to pneumonia between 8 and 12 weeks with a defective granuloma response. Atypical granulomas developed by 4 weeks expressing tow levels of MHC class II, intracellular adhesion mole cule (ICAM-1), CD11b and CD11c. Macrophages showed little signs of activati on and had low levels of acid phosphatase activity and inducible nitric oxi de synthase (INOS) expression. Despite the defective cellular recruitment, the chemokines, monocyte chemoattractant protein-1 (MCP-1) and macrophage i nflammatory protein-1 (MIP-1 alpha), were increased in broncho-alveotar lav age fluid of TNF-deficient mice. The defective host response was corrected by the transplantation of normal bone marrow cells into irradiated TNF-defi cient mice. These results demonstrate that TNF derived from hemopoietic cel ls rather than from mesenchymal origin are essential for a normal host resp onse to BCG infection. Furthermore, TNF dependent expression of adhesion mo lecules may be essential for the recruitment of mononuclear cells for the f ormation of bactericidal BCG granulomas.