Differential regulation of TNF-α production by listeriolysin-producing versus nonproducing strains of Listeria monocytogenes

M. A. Vazquez, S. C. Sicher, W. J. Wright, M. L. Proctor, S. R. Schmalzried, K. R. Stallworth, J. C. Crowley, C. Y. Lu

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19 Scopus citations


Only Listeria monocytogenes that produce listeriolysin O (LLO) elicit protective immunity. Given the importance of tumor necrosis factor cc (TNF-α) in anti-Listeria immunity, we have investigated TNF-α production by macrophages after they ingested live LLO-producing compared to LLO-nonproducing bacteria. We used two genetically engineered strains of Listeria that differed only in their ability (Ly+) or inability (Ly-) to produce LLO. Ly+ and Ly- caused the same kinetics of increased mRNA abundance for TNF-α during the first 90 min after phagocytosis. However, only Ly+ caused sustained transcription of TNF-α mRNA, and this may account for the increased release of TNF-α. The transcriptional inhibitor 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) prevented the sustained abundance of cytokine mRNA 20 h after ingestion of Ly+. In addition, nuclear run-on assays indicated sustained transcription of TNF-α genes only after ingestion of Ly+. LLO itself was not responsible for the ability of Ly+ to stimulate the sustained transcription of the TNF-α genes. Instead, LLO may allow Listeria to survive within macrophages so that other bacterial products cause sustained TNF-α gene transcription. Both Ly+ and Ly- produced molecules, isolated by 50% ammonium sulfate, that induced cytokine production. In conclusion, we now report that Ly+ causes sustained transcription of the TNF-α gene and production of TNF-α by macrophages in vitro. We speculate that the TNF-α may activate endothelium and thus allow the recruitment of T cells to sites of infection. This may contribute to the ability of only LLO-producing Listeria to induce protective immunity.

Original languageEnglish (US)
Pages (from-to)556-562
Number of pages7
JournalJournal of Leukocyte Biology
Issue number5
StatePublished - 1995


  • Bacteria
  • Hemolysin
  • Immunity
  • Macrophage

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology


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