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CD14 expression by human mononuclear phagocytes is modulated by Clostridium difficile toxin B
J C Siffert1, C D Müller, S Dumont
1LPCCNM-UPRES 2308, Illkirch, faculté de pharmacie, université Louis Pasteur, France.
Abstract:
Toxin B, an exotoxin produced by the anaerobic Gram-positive bacteria Clostridium difficile, is responsible for pseudomembranous colitis in humans. It deeply modifies morphology of cultured cells and enhances their membrane surface area, which suggests a possible alteration of membrane receptor distribution. Since toxin B and bacterial lipopolysaccharide can act synergistically on TNF-alpha production by mononuclear phagocytes, the effect of toxin B on CD14 expression was investigated using flow cytometric analysis. It was shown that monocytes overexpressed CD14 after 5 h of treatment with toxin B. In contrast, after 24 h of treatment, the percentage of CD14 monocytes decreased, although, most frequently, the remaining positive cells expressed high levels of CD14 compared with untreated cells. Macrophages treated for 5 h with toxin B overexpressed CD14, but this effect persisted for at least 24 h. Both the percentage of positive macrophages and the mean level of CD14 per cell were increased. Thus toxin B can modulate expression of CD14 and its modulation depends on the differentiation status and maybe on the activation state, since some individual variations were observed in monocyte response to toxin.
Insights
Clostridium difficile Toxin B alters CD14 expression on immune cells. Monocytes and macrophages show increased CD14 levels, but the effect varies with cell type and treatment duration.
Area of Science:
- Microbiology
- Immunology
- Cell Biology
Background:
- Clostridium difficile Toxin B causes pseudomembranous colitis.
- Toxin B alters cell morphology and membrane surface area.
- Toxin B and lipopolysaccharide synergistically stimulate TNF-alpha production.
Purpose of the Study:
- Investigate the effect of Toxin B on CD14 expression.
- Analyze CD14 modulation in monocytes and macrophages.
Main Methods:
- Flow cytometry was used to analyze CD14 expression.
- Monocytes and macrophages were treated with Toxin B.
Main Results:
- Toxin B treatment increased CD14 expression in monocytes after 5 hours.
- After 24 hours, monocyte CD14 expression decreased, but remaining cells showed higher levels.
- Toxin B significantly increased CD14 expression in macrophages, an effect sustained for at least 24 hours.
Conclusions:
- Toxin B modulates CD14 expression in a differentiation-dependent manner.
- The immune response to Toxin B may vary based on cell activation status.