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Updated: Aug 29, 2025
Bronchoalveolar Lavage Exosomes in Lipopolysaccharide-induced Septic Lung Injury
Published on: May 21, 2018
Human endothelial cell-derived exosomal microRNA-99a/b drives a sustained inflammatory response during sepsis by
Glenn Fitzpatrick1,2, Danielle Nader1,2, Rebecca Watkin1,2
1Cardiovascular Infection Research Group, Dublin, Ireland.
Abstract:
The pathophysiology of sepsis and its accompanying hyper-inflammatory response are key events that lead to multi-organ failure and death. A growing body of literature now suggests that the vascular endothelium plays a critical role in driving early events of sepsis progression. In this study, we demonstrate how endothelial-derived exosomes contribute to a successive pro-inflammatory phenotype of monocytes. Exosomes isolated from S. aureus infected endothelial cells drive both CD11b and MHCII expression in monocytes and contribute dysregulated cytokine production. Conversely, healthy endothelial exosomes had no major effect. microRNA (miRNA) profiling of exosomes identified miR-99 upregulation which we hypothesised as driving this phenotypic change through mechanistic target of rapamycin (mTOR). Knockdown of mTOR with miR-99a and miR-99b mimetics in S. aureus infected monocytes increased IL-6 and decreased IL-10 production. Interestingly, inhibition of miRNAs with antagomirs has the opposing effect. Collectively, endothelial exosomes are driving a pro-inflammatory phenotype in monocytes through dysregulated expression of miR-99a and miR-99b.
Insights
Endothelial exosomes from Staphylococcus aureus infections promote a pro-inflammatory monocyte response. These exosomes, containing miR-99, dysregulate cytokine production via mechanistic target of rapamycin (mTOR) signaling.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Sepsis pathophysiology involves hyper-inflammation and multi-organ failure.
- The vascular endothelium is increasingly recognized for its role in early sepsis progression.
- Endothelial-derived exosomes are implicated in intercellular communication during infection.
Purpose of the Study:
- To investigate the role of endothelial-derived exosomes in sepsis-induced monocyte activation.
- To identify specific molecular mechanisms by which exosomes modulate monocyte inflammatory responses.
- To explore the involvement of microRNAs (miRNAs) and mechanistic target of rapamycin (mTOR) signaling.
Main Methods:
- Isolation and characterization of exosomes from Staphylococcus aureus-infected and healthy endothelial cells.
- Treatment of monocytes with isolated exosomes to assess phenotypic and cytokine production changes.
- miRNA profiling of exosomes and manipulation of miR-99 and mTOR pathways in monocytes.
Main Results:
- Exosomes from S. aureus-infected endothelial cells induced CD11b and MHCII expression and dysregulated cytokine production in monocytes.
- miR-99 upregulation was identified in exosomes from infected endothelial cells.
- Modulation of miR-99 and mTOR pathways significantly altered IL-6 and IL-10 production in monocytes.
Conclusions:
- Endothelial-derived exosomes contribute to a pro-inflammatory monocyte phenotype during sepsis.
- Dysregulated expression of miR-99a and miR-99b within exosomes drives these changes via mTOR.
- Targeting exosomal miRNAs presents a potential therapeutic strategy for sepsis-induced inflammation.
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