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In Vitro and Animal Studies of Human Natural Killer Cell-Derived Exosomes for the Treatment of Otitis Media
Zirui Zhao1,2, Liqin Wang1,2, Zhen Guo3
1Department of Otorhinolaryngology, ENT Institute, and NHC Key Laboratory of Hearing Medicine, Eye and ENT Hospital, Fudan University, Shanghai, 200031, China.
Abstract:
Otitis media is an infection of the middle ear mainly caused by bacteria, and current treatments rely heavily on antibiotics. However, the emergence of antibiotic-resistant bacterial strains seriously affects their efficacy. In our study, we found that extracellular vesicles (EVs) derived from human natural killer cells (NKs) inhibit the proliferation of both standard and levofloxacin (LVX)-resistant strains of Staphylococcus aureus in a dose-dependent manner. Moreover, compared to LVX, EVs were more effective at reducing effusion and rescuing hearing thresholds in animal models. For LVX-sensitive strains, EVs were significantly more effective in terms of curative time but not curative rate. For LVX-resistant strains, EVs were significantly more effective in terms of both curative rate and curative time when applied alone or applied jointly with LVX. In summary, we found that NK EVs are highly effective in treating otitis media, providing an alternative approach for treating this common disease.
Insights
Human natural killer cell extracellular vesicles (NK EVs) show promise in treating otitis media, effectively inhibiting bacteria and improving outcomes in animal models, offering an alternative to antibiotics.
Area of Science:
- Immunology
- Microbiology
- Otolaryngology
Background:
- Otitis media is a common middle ear infection primarily treated with antibiotics.
- Antibiotic resistance in bacteria like Staphylococcus aureus compromises current treatment efficacy.
Purpose of the Study:
- To investigate the efficacy of extracellular vesicles (EVs) from human natural killer cells (NKs) in treating otitis media.
- To compare the effectiveness of NK EVs with levofloxacin (LVX) against standard and resistant bacterial strains.
Main Methods:
- In vitro studies assessing the dose-dependent inhibition of Staphylococcus aureus proliferation by NK EVs.
- In vivo animal models evaluating the reduction of effusion and rescue of hearing thresholds.
- Comparative analysis of curative rates and times for sensitive and resistant strains.
Main Results:
- NK EVs demonstrated dose-dependent inhibition of both standard and levofloxacin-resistant Staphylococcus aureus.
- EVs were more effective than LVX in reducing effusion and improving hearing in animal models.
- EVs significantly improved curative time for sensitive strains and both curative rate and time for resistant strains, alone or combined with LVX.
Conclusions:
- Human NK EVs represent a potent therapeutic strategy for otitis media.
- NK EVs offer a promising alternative to conventional antibiotic treatments, particularly against resistant bacterial strains.

