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Legionella pneumophila induced tumor necrosis factor production in permissive versus nonpermissive macrophages
1Department of Medical Microbiology and Immunology, University of South Florida College of Medicine, Tampa 33612.
Abstract:
The ability of an opportunistic intracellular bacterial pathogen, Legionella pneumophila, to induce tumor necrosis factor (TNF) in macrophages from susceptible A/J or resistant BDF1 and BALB/c mice was determined. Cultures of peritoneal elicited macrophages from these mouse strains produced TNF in response to the Legionella. The TNF levels produced by the macrophages stimulated with either heat-killed Legionella vaccine or lipopolysaccharide were similar and dose dependent, although the amount of TNF produced by macrophages from permissive A/J mice was 2- to 4-fold higher than that produced by macrophages from the nonpermissive mice. Similar differences in TNF levels occurred when macrophages from either permissive or non-permissive mice were infected with viable Legionella. The TNF levels produced by the A/J mouse macrophages increased as a function of time after infection, with a peak of activity on Day 1 or 2, depending upon the initial concentration of the bacteria. Infection of the A/J mouse macrophages with avirulent Legionella resulted in induced levels comparable to those induced by a virulent strain. Although it is widely believed that TNF production by mouse macrophages is related to resistance to infections, the results of this study did not show a relationship between TNF production by macrophages in vitro and resistance versus susceptibility of the macrophage donor mouse strain to Legionella infection.
Insights
Tumor necrosis factor (TNF) production by macrophages varied with mouse strain, with higher levels observed in susceptible A/J mice. This study found no direct link between macrophage TNF production and resistance to Legionella pneumophila infection.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Legionella pneumophila is an opportunistic intracellular bacterial pathogen.
- Tumor necrosis factor (TNF) is a key cytokine in immune responses.
- Macrophage TNF production is often linked to resistance against infections.
Purpose of the Study:
- To determine the ability of Legionella pneumophila to induce TNF in macrophages from different mouse strains.
- To investigate the relationship between mouse strain susceptibility and TNF production.
- To explore the correlation between in vitro TNF production and in vivo resistance to Legionella infection.
Main Methods:
- Culturing peritoneal macrophages from susceptible (A/J) and resistant (BDF1, BALB/c) mice.
- Stimulating macrophages with heat-killed Legionella vaccine, lipopolysaccharide, or viable Legionella.
- Measuring TNF levels produced by macrophages over time post-infection.
Main Results:
- Macrophages from all tested mouse strains produced TNF in response to Legionella.
- Macrophages from susceptible A/J mice produced 2- to 4-fold higher TNF levels compared to resistant strains.
- TNF production increased over time after infection, peaking at Day 1 or 2.
- Both virulent and avirulent Legionella strains induced comparable TNF levels.
Conclusions:
- Macrophage TNF production in response to Legionella pneumophila is influenced by mouse strain genetics.
- Contrary to common belief, this study did not find a direct correlation between in vitro macrophage TNF production and host resistance to Legionella infection.