Impairment of growth of Listeria monocytogenes in THP-1 macrophages by granulocyte macrophage colony-stimulating factor: release of tumor necrosis factor-alpha and nitric oxide

Carryn, Stéphane;Van de Velde, Sébastien;Van Bambeke, Françoise;Mingeot-Leclercq, Marie-Paule;Tulkens, Paul M.
(2004) The Journal of Infectious Diseases — Vol. 189, n° 11, p. 2101-2109 (2004)

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Authors
  • Carryn, StéphaneUCLouvain
    Author
  • Van de Velde, SébastienUCLouvain
    Author
  • Van Bambeke, Françoiseorcid-logoUCLouvain
    Author
  • Mingeot-Leclercq, Marie-PauleUCLouvain
    Author
  • Tulkens, Paul M.UCLouvain
    Author
Abstract
BACKGROUND: Listeria monocytogenes tends to survive in phagocytes. Granulocyte macrophage colony-stimulating factor (GM-CSF) protects mice against L. monocytogenes infection, and mice knocked out for the GM-CSF gene are more susceptible to these infections. METHODS: THP-1 cells were used to characterize the GM-CSF receptor (binding isotherms; STAT5 phosphorylation), measure the intracellular growth of L. monocytogenes (5 h after phagocytosis), examine the influence of a 24-h incubation with GM-CSF before infection, measure the production of tumor necrosis factor (TNF)-alpha and the expression of nitric oxide synthase (iNOS), and evaluate the influence of anti-GM-CSF receptor (GM-CSFR alpha ) and anti-TNF-alpha antibodies and the addition of N(omega)-nitro-L-arginine methyl ester (L-NAME) and catalase. RESULTS: THP-1 cells display functional GM-CSFR alpha. GM-CSF impairs the intracellular growth of L. monocytogenes to approximately 65% of its value in unstimulated cells. This effect is abolished by anti-GM-CSFR alpha, anti-TNF-alpha antibodies, and catalase (and, to a lesser extent, by L-NAME). GM-CSF stimulates the release of TNF-alpha and the expression of iNOS. TNF-alpha added to unstimulated cells (even in large amounts) does not fully reproduce the impairment in the growth of L. monocytogenes caused by GM-CSF. CONCLUSIONS: GM-CSF impairs the intracellular growth of L. monocytogenes by a synergistic action of the GM-CSF-triggered release of autocrine TNF-alpha and hydrogen peroxide and the production of NO (associated with the stimulation of the expression of iNOS).
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Carryn, S., Van de Velde, S., Van Bambeke, F., Mingeot-Leclercq, M.-P., & Tulkens, P. M. (2004). Impairment of growth of Listeria monocytogenes in THP-1 macrophages by granulocyte macrophage colony-stimulating factor: release of tumor necrosis factor-alpha and nitric oxide. The Journal of Infectious Diseases, 189(11), 2101-2109. https://doi.org/10.1086/420848 (Original work published 2004)