Membrane TNF confers protection to acute mycobacterial infection

• Main Authors: Yeremeev Vladimir, Grivennikov Sergei I, Dambuza Ivy, Allie Nasiema, Fremond Cecile, Quesniaux Valerie FJ, Jacobs Muazzam, Ryffel Bernhard
• Format: Article
• Language: English
• Published: BMC 2005-11-01
• Series: Respiratory Research
• Subjects: Mycobacterium tuberculosis H37Rv; membrane TNF; TNF-deficiency; T cell recruitment; granuloma
• Online Access: http://respiratory-research.com/content/6/1/136

<p>Abstract</p> <p>Background</p> <p>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).</p> <p>Methods</p> <p>C57BL/6, TNF KO and mem-TNF mice were infected with <it>M. tuberculosis </it>H37Rv (<it>Mtb </it>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.</p> <p>Results</p> <p>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 <it>Mtb </it>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 <it>Mtb </it>infection in TNF-KO mice.</p> <p>Conclusion</p> <p>Membrane expressed TNF is sufficient to allow cell-cell signalling and control of acute <it>Mtb </it>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.</p>