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Updated: Dec 4, 2025
Legionella pneumophila Outer Membrane Vesicles: Isolation and Analysis of Their Pro-inflammatory Potential on Macrophages
Published on: February 22, 2017
MiR-26a targets EphA2 to resist intracellular Listeria monocytogenes in macrophages
Jiale Zhang1, Jiangbei Yuan2, Liting Wang3
1School of Pharmaceutical Sciences and Innovative Drug Research Center, Chongqing University, Chongqing, 401331, China.
Abstract:
At infection sites, macrophages are sentinels that resist and destroy various pathogens, through direct phagocytosis. In macrophages, microRNAs play a variety of crucial roles, the most striking of which is the regulation of the ability of the host cell to resist infection. However, the underlying mechanisms associated with the anti-infection effects mediated by microRNAs remain largely unknown. Here, we demonstrated that miR-26a is downregulated during infection by Listeria monocytogenes (Lm). In miR-26a overexpressing mice, the Lm bacterial burden of liver and spleen decreased significantly within 72 h of infection, compared with that in control mice. Subsequently, RNA sequencing (RNA-seq) data suggested that miR-26a may attenuate the survival of Lm by targeting the Ephrin receptor tyrosine kinase A2 (EphA2). The knockdown of EphA2 in RAW264.7 macrophage cells resulted in decreased intracellular Lm burden. Taken together, these findings validate EphA2 as a target of miR-26a and provide a mechanism through which Lm may survive within macrophages by altering host miRNA expression.
Insights
MicroRNA miR-26a is downregulated during Listeria monocytogenes infection. Upregulating miR-26a reduces bacterial burden by targeting Ephrin receptor tyrosine kinase A2 (EphA2) in macrophages.
Area of Science:
- Immunology
- Molecular Biology
- Microbiology
Background:
- Macrophages are critical immune cells that phagocytose pathogens.
- MicroRNAs (miRNAs) regulate host-pathogen interactions and infection resistance.
- Mechanisms of miRNA-mediated anti-infection effects are not fully understood.
Purpose of the Study:
- To investigate the role of microRNA miR-26a in Listeria monocytogenes (Lm) infection.
- To elucidate the molecular mechanisms underlying miR-26a's anti-infective properties.
Main Methods:
- Studied miR-26a expression levels in Lm-infected macrophages.
- Utilized miR-26a overexpressing mice to assess bacterial burden.
- Employed RNA sequencing (RNA-seq) to identify miR-26a targets.
- Performed knockdown experiments of the target gene in macrophage cell lines.
Main Results:
- miR-26a expression was found to be downregulated during Lm infection.
- Overexpression of miR-26a in mice led to a significant reduction in Lm bacterial burden in the liver and spleen.
- RNA-seq identified Ephrin receptor tyrosine kinase A2 (EphA2) as a direct target of miR-26a.
- Knockdown of EphA2 in macrophages decreased intracellular Lm burden.
Conclusions:
- miR-26a plays a protective role against Listeria monocytogenes infection.
- EphA2 is a validated target of miR-26a, mediating its anti-bacterial effects.
- Lm survival within macrophages may involve the modulation of host miRNA expression, specifically the downregulation of miR-26a.
