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Updated: Jun 13, 2025
Legionella pneumophila Outer Membrane Vesicles: Isolation and Analysis of Their Pro-inflammatory Potential on Macrophages
Published on: February 22, 2017
Legionella pneumophila modulates macrophage functions through epigenetic reprogramming via the C-type lectin receptor
Felix Stegmann1,2, Christina Diersing1,2, Bernd Lepenies1,2
1Institute for Immunology, University of Veterinary Medicine Hannover, 30559 Hanover, Lower Saxony, Germany.
Abstract:
Legionella pneumophila is a pathogen which can lead to a severe form of pneumonia in humans known as Legionnaires disease after replication in alveolar macrophages. Viable L. pneumophila actively secrete effector molecules to modulate the host's immune response. Here, we report that L. pneumophila-derived factors reprogram macrophages into a tolerogenic state, a process to which the C-type lectin receptor Mincle (CLEC4E) markedly contributes. The underlying epigenetic state is characterized by increases of the closing mark H3K9me3 and decreases of the opening mark H3K4me3, subsequently leading to the reduced secretion of the cytokines TNF, IL-6, IL-12, the production of reactive oxygen species, and cell-surface expression of MHC-II and CD80 upon re-stimulation. In summary, these findings provide important implications for our understanding of Legionellosis and the contribution of Mincle to reprogramming of macrophages by L. pneumophila.
Insights
Legionella pneumophila reprograms macrophages into a tolerogenic state, involving Mincle (CLEC4E) and epigenetic changes. This impairs immune responses, impacting Legionnaires disease understanding.
Area of Science:
- Immunology
- Microbiology
- Epigenetics
Background:
- Legionella pneumophila causes Legionnaires disease by replicating in macrophages.
- The pathogen modulates host immune responses via secreted effector molecules.
Purpose of the Study:
- To investigate how L. pneumophila factors reprogram macrophages.
- To elucidate the role of Mincle (CLEC4E) in this reprogramming process.
Main Methods:
- Analysis of macrophage reprogramming induced by L. pneumophila factors.
- Assessment of epigenetic modifications (H3K9me3, H3K4me3) in reprogrammed macrophages.
- Evaluation of cytokine secretion and cell surface marker expression upon re-stimulation.
Main Results:
- L. pneumophila factors induce a tolerogenic state in macrophages.
- Mincle (CLEC4E) significantly contributes to this reprogramming.
- Epigenetic changes include increased H3K9me3 and decreased H3K4me3.
- Reprogrammed macrophages show reduced TNF, IL-6, IL-12, ROS production, and lower MHC-II/CD80 expression.
Conclusions:
- L. pneumophila actively reprograms macrophages to a tolerogenic state.
- Mincle plays a crucial role in mediating this macrophage reprogramming.
- Epigenetic modifications underlie the observed suppression of immune responses in Legionellosis.
