Bacterial extracellular vesicles reduce inflammation in neutrophilic asthma

Micrococcus luteus-derived bacterial extracellular vesicles (MIEVs) inhibited airway inflammation in patients with neutrophilic asthma, Korean researchers said. Micrococcus luteus is a commensal bacterium commonly found in the skin, mouth, nose, and upper respiratory tract.

The research team, led by Professor Park Hae-sim at the Department of Allergy and Clinical Immunology of Ajou University Hospital and MD Healthcare CEO Kim Yoon-keun, said on Wednesday that their study confirmed MIEVs’ inhibitory effect on airway inflammation in  patients with neutrophilic asthma.

The research team divided asthma patients into 10 with eosinophilic asthma and another 10 with  neutrophilic asthma. Then, they measured IgG4 specific to MIEVs in serum from each patient group and analyzed its association with lung function.

The results showed that the neutrophilic asthma patient group demonstrated low levels of MIEV-specific IgG4, which were associated with lower lung function. IgG4 is a specific indicator for long-term and repeated exposure to external antigens. The study found that patients with neutrophilic asthma were exposed to fewer MIEVs than those with eosinophilic asthma.

Based on these findings, the research team conducted an animal study. In the asthmatic mice model, intranasally injected MIEVs markedly reduced airway inflammation and resistance. The research team also confirmed that MIEVs regulated miRNA (micro RNA) that suppresses the activation of immune cells involved in the exacerbation of neutrophilic asthma.

In particular, MIEVs inhibited the NLR)3 inflammasome of monocytes by regulating hsa-miR-4517, present in airway epithelial cells, thereby lowering the secretion of IL-1β and the production of IL-17 in type 3 innate lymphocytes. In eosinophilic asthma, previously known as allergic asthma, its pathological mechanism and several biological agents have been identified. However, patients with neutrophilic asthma do not respond well to general asthma treatments, including steroids.

Association between miRNAs in plasma and inflammatory status in asthmatic patients

Fig. 6

a Expression of miRNAs in the plasma of asthmatic patients compared to HCs. b Levels of IL-22 in plasma in comparison between patients with EA and those with NA. Data are represented as the means ± SDs. P values were obtained by Student’s t-test. c Correlation between miRNA expression and IL-22 levels. Data are presented as the Pearson correlation coefficient r (P value). d Gating strategy of ILC isolation. e Expression of GATA-3, ROR-γt, and IL-22 in ILCs. f IL-22 levels released from ILCs treated with or without MlEVs in the presence of monocytes. Data are represented as the means ± SDs. P values were obtained by Student’s t test. g Schematic of MlEVs inhibiting airway inflammation. ILC innate lymphoid cell, GATA3 GATA-binding protein 3, Mo monocyte.

However, as the incidence of neurophilic asthma has been steadily rising in Korea, the need for introducing a new immunomodulator has increased. With the development of metagenomics analysis technology, it has been revealed that the human microbiome can prevent or control the exacerbation of asthma. The latest study is meaningful because it identified the anti-inflammatory effect of MIEVs in asthma and their potential as a new therapeutic agent, the research team said.

Professor Park, who is the corresponding author, expected that MIEVs could be used in combination with existing treatments as a selective immunomodulator to maximize the therapeutic effect in asthma.

Source – Korea Biomedical Review

Sim S, Lee DH, Kim KS, Park HJ, Kim YK, Choi Y, Park HS. (2023) Micrococcus luteus-derived extracellular vesicles attenuate neutrophilic asthma by regulating miRNAs in airway epithelial cells. Exp Mol Med 55(1):196-204. [article]

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