Related Experiment Videos
Studies on cytokine activation of listericidal activity in murine macrophages
1Bioscience I, ICI, Pharmaceuticals, Mereside, Alderley Park, Macclesfield, Cheshire, United Kingdom.
Abstract:
The ability of a variety of soluble factors, alone or in combination, to endow murine resident peritoneal macrophages with listericidal activity was assessed. Inhibition of growth and (or) killing of Listeria in infected macrophages was determined by the uptake of [3H]uracil following lysis of the infected macrophage monolayers. Interferon-gamma was shown to induce modest listericidal activity in murine resident macrophages as compared with untreated monolayers. Treatment with tumour necrosis factor alpha also induced significant listericidal activity in this system. Among other cytokines tested, IL-4 induced an ability to inhibit growth of Listeria in resident macrophages. The ability of cytokines tested, IL-4 induced an ability to inhibit growth of Listeria in resident macrophages. The ability of cytokines to act in an additive or synergistic fashion with IFN-gamma was also investigated. Combinations of IFN-gamma and IL-4 and IFN-gamma and IL-2 induced listericidal activity not greater than that seen with IFN-gamma alone. IFN-gamma and TNF-alpha were shown to increase bactericidal activity in an additive fashion. However, elicited macrophages were shown to spontaneously exert a significant listericidal activity that was not enhanced by cytokine treatment. Collectively, these findings show that cytokine treatment induced rather modest enhancement in listericidal activity in murine resident peritoneal macrophages and no enhancement whatsoever in elicited macrophages. Thus, in in vivo situations where Listeria organisms are completely cleared from the infected organs, mechanisms other than lymphokine-induced listericidal activity of resident macrophages would seem to be operating.
Insights
Cytokine treatment modestly enhanced listericidal activity in resident macrophages against Listeria. However, elicited macrophages showed no enhancement, suggesting other mechanisms clear Listeria infections in vivo.
Area of Science:
- Immunology
- Cell Biology
- Microbiology
Background:
- Macrophages play a crucial role in host defense against intracellular pathogens like Listeria.
- Soluble factors, including cytokines, are known to modulate macrophage functions.
- Understanding cytokine-induced macrophage activation is key to developing strategies against Listeria infections.
Purpose of the Study:
- To assess the listericidal activity of murine resident peritoneal macrophages upon treatment with various soluble factors.
- To investigate the additive or synergistic effects of combined cytokines on macrophage listericidal function.
- To compare the cytokine responsiveness of resident versus elicited macrophages.
Main Methods:
- Murine resident peritoneal macrophages were infected with Listeria.
- Listericidal activity was quantified by measuring [3H]uracil uptake after macrophage lysis.
- Macrophages were treated with individual cytokines (Interferon-gamma, Tumor Necrosis Factor-alpha, IL-4, IL-2) and combinations thereof.
Main Results:
- Interferon-gamma (IFN-γ) induced modest listericidal activity in resident macrophages.
- Tumor Necrosis Factor-alpha (TNF-α) significantly enhanced listericidal activity.
- Combinations of IFN-γ with IL-4 or IL-2 did not improve activity beyond IFN-γ alone.
- IFN-γ and TNF-α showed additive effects on bactericidal activity.
- Elicited macrophages exhibited spontaneous listericidal activity, unaffected by cytokine treatment.
Conclusions:
- Cytokine treatment provides only a modest enhancement of listericidal activity in resident macrophages.
- Elicited macrophages do not show enhanced listericidal activity upon cytokine stimulation.
- Mechanisms beyond lymphokine-induced macrophage activity are likely responsible for Listeria clearance in vivo.