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Published on: March 16, 2018
c-fos and tumor necrosis factor gene expression in Leishmania donovani-infected macrophages
1Institute of Parasitology, McGill University, Macdonald College, Ste-Anne de Bellevue, Quebec, Canada.
Abstract:
Leishmania donovani is an obligate intracellular protozoan which resides in macrophages and impairs a number of macrophage functions. We have undertaken to study this host cell-parasite interaction by examining the ability of L. donovani to impair the transmission of information from the cell surface to the nucleus and thus influence normal gene expression. We demonstrate that, in response to lipopolysaccharide, expression of both the c-fos and tumor necrosis factor genes was impaired in L. donovani-infected macrophages. Indomethacin reversed the parasite-mediated downregulation of the tumor necrosis factor gene but not the c-fos gene, suggesting that the impaired expression of these two genes occurred through different mechanisms. Direct stimulation of protein kinase C with oleoyl-2-acetoyl-3-glycerol did not abrogate inhibition of c-fos gene expression by L. donovani; however, L929 cell-conditioned medium induced a similar level of c-fos gene expression in both infected and noninfected macrophages. Impairment of c-fos gene expression by L. donovani thus appeared to be selective, depending on the external stimuli used to induce its expression. These data argue that L. donovani was capable of impairing macrophage gene expression in a selective rather than a general manner.
Insights
Leishmania donovani impairs macrophage gene expression selectively. This parasite affects c-fos and tumor necrosis factor gene expression differently, depending on external stimuli.
Area of Science:
- Immunology
- Molecular Biology
- Parasitology
Background:
- Leishmania donovani is an obligate intracellular protozoan.
- It resides within macrophages, impairing their functions.
- Understanding host cell-parasite interactions is crucial for disease control.
Purpose of the Study:
- To investigate how Leishmania donovani affects host cell signaling pathways.
- To determine the impact of L. donovani infection on macrophage gene expression.
- To elucidate the mechanisms underlying parasite-mediated gene regulation.
Main Methods:
- Macrophages were infected with Leishmania donovani.
- Gene expression of c-fos and tumor necrosis factor was analyzed.
- Stimulation with lipopolysaccharide and other agents was employed.
- The effect of indomethacin and protein kinase C stimulation was assessed.
Main Results:
- L. donovani infection impaired c-fos and tumor necrosis factor gene expression in response to lipopolysaccharide.
- Indomethacin reversed tumor necrosis factor gene downregulation but not c-fos.
- Inhibition of c-fos gene expression was selective, varying with external stimuli.
- Protein kinase C stimulation did not overcome L. donovani's inhibition of c-fos.
Conclusions:
- Leishmania donovani selectively impairs macrophage gene expression.
- The parasite influences distinct signaling pathways for different genes.
- These findings offer insights into host-parasite molecular interactions.
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