Mice deficient for the 55 kd tumor necrosis factor receptor are resistant to endotoxic shock, yet succumb to L. monocytogenes infection

Cell. 1993 May 7;73(3):457-67. doi: 10.1016/0092-8674(93)90134-c.


The multiple biological activities of tumor necrosis factor (TNF) are mediated by two distinct cell surface receptors of 55 kd (TNFRp55) and 75 kd (TNFRp75). Using gene targeting, we generated a TNFRp55-deficient mouse strain. Cells from TNFRp55-/-mutant mice lack expression of TNFRp55 but display normal numbers of high affinity TNFRp75 molecules. Thymocyte development and lymphocyte populations are unaltered, and clonal deletion of potentially self-reactive T cells is not impaired. However, TNF signaling is largely abolished, as judged by the failure of TNF to induce NF-kappa B in T lymphocytes from TNFRp55-deficient mice. The loss of TNFRp55 function renders mice resistant to lethal dosages of either lipopolysaccharides or S. aureus enterotoxin B. In contrast, TNFRp55-deficient mice are severely impaired to clear L. monocytogenes and readily succumb to infection. Thus, the 55 kd TNFR plays a decisive role in the host's defense against microorganisms and their pathogenic factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Nucleus / metabolism
  • Cloning, Molecular
  • Humans
  • Immunity, Innate / genetics*
  • Kinetics
  • Lipopolysaccharides / toxicity
  • Listeriosis / immunology*
  • Listeriosis / physiopathology
  • Liver / pathology
  • Lymphocytes / metabolism
  • Mice
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Molecular Weight
  • NF-kappa B / metabolism
  • Oligodeoxyribonucleotides
  • Polymerase Chain Reaction / methods
  • Radioligand Assay
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / genetics*
  • Receptors, Cell Surface / metabolism
  • Receptors, Tumor Necrosis Factor
  • Shock, Septic / immunology*
  • Shock, Septic / pathology
  • Transfection
  • Tumor Necrosis Factor-alpha / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology


  • Lipopolysaccharides
  • NF-kappa B
  • Oligodeoxyribonucleotides
  • Receptors, Cell Surface
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha