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Mice lacking the tumour necrosis factor receptor 1 are resistant to IMF-mediated toxicity but highly susceptible to infection by Listeria monocytogenes

Nature volume 364, pages 798–802 (1993)Cite this article

Abstract

TUMOUR necrosis factor (TNF), jointly referring to TNFα and TNFβ , is a central mediator of immune and inflammatory responses; its activities are mediated by two distinct receptors, TNFR1 (p55) and TNFR2 (p75) (reviewed in refs 1–3). The cyto-plasmic domains of the TNFRs are unrelated, suggesting that they link to different intracellular signalling pathways4. Although most TNF responses have been assigned to one or the other of the TNF receptors (mostly TNFR1), there is no generally accepted model for the physiological role of the two receptor types. To investigate the role of TNFR1 in beneficial and detrimental activities of TNF, we generated TNFR1-deficient mice by gene targeting. We report here that mice homozygous for a disrupted Tnfr l allele (Tnfr10) are resistant to the lethal effect of low doses of lipopolysaccharide after sensitization with D-galactosamine, but remain sensitive to high doses of lipopolysaccharide. The increased susceptibility of Tnfr10Tnfr10 mutant mice to infection with the facultative intracellular bacterium Listeria monocytogenes indicates an essential role of TNF in nonspecific immunity.

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Author information

Author notes

  1. Joachim Rothe

    Present address: Imperial Cancer Research Fund, Genome Analysis Laboratory, Lincoln's Inn Fields 44, London, WC2A 3PX, UK

  2. Frank Köntgen

    Present address: The Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Parkville, Victoria, 3050, Australia

  3. Michael Steinmetz

    Present address: Preclinical Research, F. Hoffmann-La Roche Inc., Nutley, New Jersey, 07110, USA

  4. Horst Bluethmann: To whom correspondence should be addressed

Authors and Affiliations

  1. Department of Biology, Pharmaceutical Research New Technologies, Hoffmann-La Roche Ltd, Basel, CH-4002, Switzerland

    Joachim Rothe, Werner Lesslauer, Hansruedi Lötscher, Yolande Lang, Pascale Koebel, Frank Köntgen, Michael Steinmetz & Horst Bluethmann

  2. Institute of Experimental Immunology University of Zürich, Zürich, CH-8057, Switzerland

    Alana Althage & Rolf Zinkernagel

Authors
  1. Joachim Rothe
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  2. Werner Lesslauer
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  9. Michael Steinmetz
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  10. Horst Bluethmann
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Rothe, J., Lesslauer, W., Lötscher, H. et al. Mice lacking the tumour necrosis factor receptor 1 are resistant to IMF-mediated toxicity but highly susceptible to infection by Listeria monocytogenes. Nature 364, 798–802 (1993). https://doi.org/10.1038/364798a0

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