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The HL-60 model for the interaction of human macrophages with the Legionnaires' disease bacterium
A Marra1, M A Horwitz, H A Shuman
1Department of Microbiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032.
Abstract:
The facultative intracellular pathogen, Legionella pneumophila, multiplies within and kills human monocytes and alveolar macrophages. We show that L. pneumophila strain Philadelphia-1 infects, multiplies within and kills the promyelocyte HL-60 cell line after its differentiation into macrophage-like cells. The characteristics of the interaction between L. pneumophila and differentiated HL-60 cells closely resemble those between L. pneumophila and human peripheral blood monocytes. With both cell types, C receptors and serum C mediate attachment of L. pneumophila, which are taken up by coiling phagocytosis. The replicative phagosome is lined with ribosomes; intracellular multiplication is iron-dependent; and replicating bacteria ultimately destroy the host cell. As in human monocytes, an avirulent mutant derivative of L. pneumophila Philadelphia-1, 25D, does not replicate in and is not cytopathic for differentiated HL-60 cells. Differentiated HL-60 cells therefore provide a convenient and faithful model for the study of L. pneumophila-mononuclear phagocyte interaction.
Insights
Legionella pneumophila infects and kills human immune cells. Differentiated HL-60 cells serve as a reliable model to study this interaction, mimicking how the bacteria infect and replicate within monocytes.
Area of Science:
- Microbiology
- Immunology
- Cell Biology
Background:
- Legionella pneumophila is a facultative intracellular pathogen.
- It infects and destroys human monocytes and alveolar macrophages.
Purpose of the Study:
- To investigate the interaction between L. pneumophila and differentiated HL-60 cells.
- To determine if differentiated HL-60 cells can serve as a model for L. pneumophila-mononuclear phagocyte interactions.
Main Methods:
- Infection of differentiated HL-60 cells with L. pneumophila strain Philadelphia-1.
- Comparison of cellular interactions with those observed in human monocytes.
- Assessment of bacterial replication, cytopathicity, and dependence on iron.
Main Results:
- L. pneumophila infects, replicates within, and kills differentiated HL-60 cells.
- The interaction characteristics mirror those with human monocytes, involving C receptors and serum C for attachment via coiling phagocytosis.
- Intracellular multiplication is iron-dependent, and an avirulent mutant (25D) did not replicate or cause cytopathy.
Conclusions:
- Differentiated HL-60 cells provide a convenient and accurate model for studying Legionella pneumophila interactions with mononuclear phagocytes.
- This model facilitates research into the mechanisms of L. pneumophila pathogenesis.