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Enhanced growth restriction of Legionella pneumophila in endotoxin-treated macrophages
K Egawa1, T W Klein, Y Yamamoto
1Department of Medical Microbiology and Immunology, University of South Florida College of Medicine, Tampa 33612.
Abstract:
Macrophages from A/J mice are permissive for growth of Legionella pneumophila, an intracellular opportunistic pathogen that grows preferentially in macrophages. Macrophages from other mouse strains are highly resistant to growth of Legionella. In the present study, it was found that macrophages from A/J mice are readily activated by pretreatment with lipopolysaccharide (LPS), so that the cells do not permit Legionella to replicate in vitro, as occurs when untreated macrophages from A/J mice are cultured with these organisms for 48 hr. The augmentation of Legionella growth inhibition by LPS-activated macrophages from nonpermissive BDF1 mice also occurred. After in vitro infection, there was a 1000-fold increase in the number of Legionella in A/J macrophages and approximately a 10-fold increase in BDF1 macrophages, but LPS treatment of macrophages from either strain resulted in marked growth restrictions. This suppression was both dose dependent as well as dependent upon the time of addition of the LPS to the macrophages. Furthermore, the lipid A component of LPS was found to be as effective as the intact LPS in activating macrophages to inhibit the intracellular growth of Legionella. Further studies concerning the mechanisms involved are clearly warranted and in progress.
Insights
Lipopolysaccharide (LPS) activates mouse macrophages, preventing Legionella pneumophila growth. This finding is crucial for understanding macrophage immune responses and developing strategies against this opportunistic pathogen.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Macrophages are key immune cells involved in host defense against intracellular pathogens.
- Legionella pneumophila is an opportunistic pathogen that preferentially infects and replicates within macrophages.
- Mouse macrophage susceptibility to L. pneumophila varies significantly between strains, with A/J mice being permissive and others resistant.
Purpose of the Study:
- To investigate the effect of lipopolysaccharide (LPS) activation on macrophage permissiveness to Legionella pneumophila growth.
- To determine if LPS pre-treatment can render normally permissive macrophages resistant to L. pneumophila replication.
- To explore the role of LPS dose and timing of addition in modulating macrophage anti-Legionella activity.
Main Methods:
- Macrophages from A/J (permissive) and BDF1 (non-permissive) mice were cultured in vitro.
- Macrophages were pre-treated with varying concentrations and at different times with lipopolysaccharide (LPS).
- Cells were subsequently infected with Legionella pneumophila, and bacterial growth was quantified over 48 hours.
Main Results:
- LPS-activated macrophages from A/J mice significantly inhibited Legionella pneumophila replication, unlike untreated macrophages.
- LPS treatment also enhanced growth restriction in non-permissive BDF1 macrophages.
- Inhibition was dependent on LPS dose and timing of addition, with lipid A component showing similar efficacy to intact LPS.
Conclusions:
- Macrophage activation by LPS confers resistance to intracellular Legionella pneumophila growth.
- LPS-mediated immune modulation offers a potential strategy to control Legionella infections.
- Further research into the molecular mechanisms underlying LPS-induced anti-Legionella activity is warranted.