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Membrane TNF Confers Protection to Acute Mycobacterial Infection

Overview
Journal Respir Res
Specialty Pulmonary Medicine
Date 2005 Nov 16
PMID 16285886
Citations 28
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Abstract

Background: Tumour necrosis factor (TNF) is crucial for the control of mycobacterial infection as TNF deficient (KO) die rapidly of uncontrolled infection with necrotic pneumonia. Here we investigated the role of membrane TNF for host resistance in knock-in mice with a non-cleavable and regulated allele (mem-TNF).

Methods: C57BL/6, TNF KO and mem-TNF mice were infected with M. tuberculosis H37Rv (Mtb at 100 CFU by intranasal administration) and the survival, bacterial load, lung pathology and immunological parameters were investigated. Bone marrow and lymphocytes transfers were used to test the role of membrane TNF to confer resistance to TNF KO mice.

Results: While TNF-KO mice succumbed to infection within 4-5 weeks, mem-TNF mice recruited normally T cells and macrophages, developed mature granuloma in the lung and controlled acute Mtb infection. However, during the chronic phase of infection mem-TNF mice succumbed to disseminated infection with necrotic pneumonia at about 150 days. Reconstitution of irradiated TNF-KO mice with mem-TNF derived bone marrow cells, but not with lymphocytes, conferred host resistance to Mtb infection in TNF-KO mice.

Conclusion: Membrane expressed TNF is sufficient to allow cell-cell signalling and control of acute Mtb infection. Bone marrow cells, but not lymphocytes from mem-TNF mice confer resistance to infection in TNF-KO mice. Long-term infection control with chronic inflammation likely disrupting TNF mediated cell-cell signalling, additionally requires soluble TNF.

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References
1.
Cooper A, Roberts A, RHOADES E, Callahan J, Getzy D, Orme I . The role of interleukin-12 in acquired immunity to Mycobacterium tuberculosis infection. Immunology. 1995; 84(3):423-32. PMC: 1415123. View

2.
MacMicking J, Nathan C, Hom G, Chartrain N, Fletcher D, Trumbauer M . Altered responses to bacterial infection and endotoxic shock in mice lacking inducible nitric oxide synthase. Cell. 1995; 81(4):641-50. DOI: 10.1016/0092-8674(95)90085-3. View

3.
Flynn J, GOLDSTEIN M, Chan J, Triebold K, Pfeffer K, Lowenstein C . Tumor necrosis factor-alpha is required in the protective immune response against Mycobacterium tuberculosis in mice. Immunity. 1995; 2(6):561-72. DOI: 10.1016/1074-7613(95)90001-2. View

4.
Grell M, Douni E, Wajant H, Lohden M, Clauss M, Maxeiner B . The transmembrane form of tumor necrosis factor is the prime activating ligand of the 80 kDa tumor necrosis factor receptor. Cell. 1995; 83(5):793-802. DOI: 10.1016/0092-8674(95)90192-2. View

5.
Muller M, Eugster H, Le Hir M, Shakhov A, Di Padova F, Maurer C . Correction or transfer of immunodeficiency due to TNF-LT alpha deletion by bone marrow transplantation. Mol Med. 1996; 2(2):247-55. PMC: 2230110. View