Tumor necrosis factor alpha binding to bacteria: Evidence for a high- affinity receptor and alteration of bacterial virulence properties

G. Luo, David Niesel, R. A. Shaban, E. A. Grimm, G. R. Klimpel

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Human and murine receptors for tumor necrosis factor alpha (TNF-α) are present on most somatic cells and have been characterized and cloned. In contrast, very little is currently known about whether TNF-α can bind to pathogens and whether such binding results in important biological consequences for the infected host. We now report that a number of gram- negative bacteria have receptors for TNF-α. Using 125I-labeled TNF-α, we show that Shigella flexneri has 276 receptors for TNF-α, with a K(d) of 2.5 nM. The binding of labeled TNF-α to these bacterial receptors can be inhibited by cold TNF-α but not by cold TNF-β. Binding of 125I-TNF-α to S. flexneri was inhibited by trypsin treatment of bacterial cells or incubation at 52°C for 3 min. Monoclonal antibody to either the 55-kDa or the 75-kDa TNF-α receptor, which are present on different eukaryotic cells, had no effect on 125I-TNF-α binding to bacteria. A number of gram- negative bacteria were capable of binding 125I-TNF-α. Gram-positive bacteria bound significantly less 125I-TNF-α than gram-negative bacteria. Pretreatment of S. flexneri with TNF-α resulted in enhanced bacterial invasion of HeLa cells and enhanced uptake by human and murine macrophages. Pretreatment of HeLa cells with antibody to the 55-kDa TNF-α receptor abrogated enhanced invasion of HeLa cells by TNF-α-bacterium complexes. These results suggest that TNF-α-bacterium complexes can interact with TNF- α receptors present on eukaryotic cells. This report shows that gram- negative bacteria have receptors for TNF-α and that a virulence property of a bacterium is altered as a consequence of cytokine binding.

Original languageEnglish (US)
Pages (from-to)830-835
Number of pages6
JournalInfection and Immunity
Issue number3
StatePublished - 1993


ASJC Scopus subject areas

  • Immunology

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