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Intranasal Delivery of Bacterial Extracellular Vesicles Enables RNA Cargo Entry Into the Brain
Jae Yeong Ha1,2, So-Mi Kim1,2, Song-Yi Choi1,2
1Department of Microbiology and Immunology, School of Dentistry, Kyungpook National University, Daegu, South Korea.
Journal of Extracellular Vesicles
|June 11, 2026
Summary
Bacterial extracellular vesicles (EVs) can deliver functional RNA into the brain via neuronal transport and immune cells. This study demonstrates bacterial EVs cross the blood-brain barrier, impacting neuroimmune interactions.
Area of Science:
- Neuroscience
- Microbiology
- Immunology
Background:
- Bacterial extracellular vesicles (EVs) mediate host-microbe interactions, influencing immune responses and disease.
- The capacity of bacterial EVs to access the brain and affect host cells is largely unknown.
Purpose of the Study:
- To investigate the transport and functional delivery of engineered bacterial EVs into the brain.
- To identify the pathways and cell types involved in bacterial EV brain entry.
Main Methods:
- Intranasal administration of engineered Escherichia coli EVs (Ec EVCre) in mT/mG reporter mice.
- Single-cell RNA sequencing and imaging of olfactory regions.
- Microfluidic biochip assays with cultured sensory neurons.
- Pharmacological inhibition of EV uptake pathways.
Main Results:
- Bacterial EVs were taken up by the olfactory epithelium and delivered functional mRNA to olfactory bulb neurons.
- Neuronal and immune cells were identified as key EV targets.
- EVs undergo retrograde axonal transport via signaling endosomes in neurons.
- Phagocytic cells (neutrophils, macrophages) engulfed EVs and migrated into the brain.
Conclusions:
- Bacterial EVs can functionally deliver RNA cargo into the brain through both neuronal and immune-mediated pathways.
- These findings offer new insights into microbial access to the central nervous system and neuroimmune interactions.
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