Membrane TNF confers protection to acute mycobacterial infection

Respiratory Research

Bernhard Ryffel²  Muazzam Jacobs⁴  Valerie FJ Quesniaux²  Vladimir Yeremeev³  Sergei I Grivennikov¹  Ivy Dambuza⁴  Nasiema Allie⁴  Cecile Fremond² 

[1] Laboratory of Molecular Immunoregulation, Center for Cancer Research, National Cancer Institute-Frederick, Fort-Detrick, Frederick, MD 21702, USA;Molecular Immunology and Embryology, Centre National de la Recherche Scientifique, Orléans, France;Max Planck Institute for Infection Biology, Department of Immunology, Schumannstrabe 21/22, 10117 Berlin, Germany;Department of Immunology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa

关键词: granuloma;    T cell recruitment;    TNF-deficiency;    membrane TNF;    Mycobacterium tuberculosis H37Rv;   

Others  :  1163323
DOI  :  10.1186/1465-9921-6-136

 received in 2005-06-16, accepted in 2005-11-14,  发布年份 2005

【 摘 要 】

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.

【 授权许可】

   
2005 Fremond et al; licensee BioMed Central Ltd.

【 图 表 】

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