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Effect of ethanol on the interaction between the macrophage and Mycobacterium avium
1Kuzell Institute for Arthritis and Infectious Diseases, California Pacific Medical Center Research Institute, San Francisco 94115.
Abstract:
Chronic ethanol ingestion predisposes to tuberculosis and bacterial pneumonia. Mycobacterium avium complex organisms cause bacteremia in patients with AIDS. Human macrophages and murine Kupffer cells exposed to ethanol are more permissive towards intracellular growth of M. avium than control mononuclear phagocytes. Ethanol also has been shown to impair the ability of human macrophages and murine Kupffer cells to respond to stimulation with tumor necrosis factor (TNF) and granulocyte macrophage colony stimulating factor (GM-CSF), and to produce cytokines such as interleukin-1, interleukin-6, and TNF when properly stimulated. The impairment is dependent in part on a downregulation in the number of TNF receptors on the macrophage's membrane. Recent evidence suggests that ethanol in nonlethal concentrations induces stress-related proteins in M. avium, leading to the inhibition of intracellular pathways in the macrophage and, consequently, impairing some of its functions. In summary, ethanol acts both on the host and on the mycobacterium in a complex sequence of events that influence the outcome of the infection.
Insights
Chronic ethanol consumption weakens immune cells, increasing susceptibility to infections like tuberculosis and Mycobacterium avium complex. This occurs because alcohol impairs macrophage function and enhances bacterial survival within host cells.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Chronic ethanol ingestion is linked to increased susceptibility to opportunistic infections, including tuberculosis and bacterial pneumonia.
- Mycobacterium avium complex (MAC) bacteremia is a significant concern in patients with Acquired Immunodeficiency Syndrome (AIDS).
Purpose of the Study:
- To investigate the impact of ethanol on the interaction between host immune cells (macrophages, Kupffer cells) and Mycobacterium avium.
- To elucidate the mechanisms by which ethanol influences macrophage function and mycobacterial growth.
Main Methods:
- Exposure of human macrophages and murine Kupffer cells to ethanol.
- Assessment of intracellular growth of M. avium in ethanol-exposed versus control cells.
- Evaluation of macrophage responses to stimulation with tumor necrosis factor (TNF) and granulocyte macrophage colony stimulating factor (GM-CSF).
- Measurement of cytokine production (interleukin-1, interleukin-6, TNF) and TNF receptor expression.
Main Results:
- Ethanol-exposed macrophages and Kupffer cells were more permissive to intracellular M. avium growth.
- Ethanol impaired the response of macrophages and Kupffer cells to TNF and GM-CSF stimulation.
- Ethanol exposure led to reduced production of key cytokines (IL-1, IL-6, TNF) by stimulated macrophages.
- Downregulation of TNF receptors on the macrophage membrane contributed to impaired function.
- Nonlethal ethanol concentrations induced stress-related proteins in M. avium, inhibiting macrophage intracellular pathways.
Conclusions:
- Ethanol exerts a dual effect, impacting both the host's immune cells and the mycobacterium.
- Ethanol compromises macrophage and Kupffer cell function, increasing susceptibility to M. avium infections.
- Understanding these complex interactions is crucial for managing infections in individuals with chronic alcohol consumption.