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

J Rothe, W Lesslauer, H Lötscher, Y Lang, P Koebel… - Nature, 1993 - nature.com
J Rothe, W Lesslauer, H Lötscher, Y Lang, P Koebel, F Köntgen, A Althage, R Zinkernagel…
Nature, 1993nature.com
TUMOUR necrosis factor (TNF), jointly referring to TNF α and TNF β, 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 …
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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