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Differential effects of ethanol on permissive versus nonpermissive macrophages infected with Legionella pneumophila
Y Yamamoto1, T W Klein, H Friedman
1Department of Medical Microbiology and Immunology, University of South Florida College of Medicine, Tampa 33612.
Abstract:
The effect of ethanol treatment was studied in terms of effect on permissive versus nonpermissive macrophages for growth of Legionella pneumophila, which is an intracellular bacterium causing pneumonia in immunocompromised patients. It was found that ethanol treatment of permissive macrophages from L. pneumophila-susceptible A/J mice evinced a decrease in replication of the bacteria compared with nontreated infected macrophages. Whereas there was more than a 100-fold increase in Legionella growth over a 48-hr culture period in infected A/J mouse macrophages, treatment of the macrophages with 0.5% ethanol depressed the ability of the macrophages to be infected by Legionella approximately 45%. A lower concentration of ethanol had a lesser effect but still resulted in inhibition of the ability of the cells to replicate Legionella. In contrast to ethanol-induced inhibition of the A/J mouse macrophages to replicate Legionella, macrophages from Legionella-resistant BALB/c mice, which only minimally replicated Legionella (i.e., only a 2-fold increase or less over a 48-hr replicated Legionella (i.e., only a 2-fold increase or less over a 48-hr period), treatment with ethanol resulted in their greater replication of the Legionella. This effect was most marked with the 1.0% concentration of ethanol after 7 days of pretreatment, while the 0.5% and 0.1% concentrations of alcohol caused less enhancement of bacterial growth in the cells, but these concentrations still had a significant enhancement effect. Thus, ethanol had differing effects on growth of the opportunistic intracellular bacterium Legionella in macrophages from permissive versus nonpermissive mice. Studies on the mechanisms involved are in progress.
Insights
Ethanol inhibits Legionella pneumophila growth in permissive mouse macrophages but enhances it in nonpermissive ones. This study reveals differential effects of ethanol on bacterial replication within immune cells.
Area of Science:
- Immunology
- Microbiology
- Pharmacology
Background:
- Legionella pneumophila is an intracellular bacterium causing pneumonia, particularly in immunocompromised individuals.
- Macrophages play a crucial role in controlling intracellular bacterial infections.
- Understanding host-pathogen interactions and the influence of external agents on these interactions is vital for developing therapeutic strategies.
Purpose of the Study:
- To investigate the effect of ethanol treatment on the replication of Legionella pneumophila within permissive and nonpermissive macrophages.
- To determine if ethanol differentially impacts bacterial growth in macrophages from susceptible versus resistant mouse strains.
Main Methods:
- Primary macrophages were isolated from A/J (permissive) and BALB/c (nonpermissive) mice.
- Macrophages were treated with varying concentrations of ethanol (0.1%, 0.5%, 1.0%) for different durations.
- Infected macrophages were cultured, and Legionella pneumophila replication was quantified over 48 hours and 7 days.
Main Results:
- Ethanol treatment (0.5%) significantly reduced Legionella pneumophila replication by approximately 45% in permissive A/J mouse macrophages.
- In contrast, ethanol treatment enhanced Legionella pneumophila replication in nonpermissive BALB/c mouse macrophages, with the effect most pronounced at 1.0% ethanol after 7 days.
- Lower ethanol concentrations also showed an enhancing effect on bacterial growth in nonpermissive macrophages, indicating a dose-dependent and cell-type-specific response.
Conclusions:
- Ethanol exhibits differential effects on Legionella pneumophila replication depending on the macrophage's permissiveness to bacterial growth.
- Ethanol inhibits bacterial growth in susceptible host cells while promoting it in resistant host cells.
- Further studies are warranted to elucidate the underlying mechanisms of these contrasting effects.