Immunomodulatory Activity of Extracellular Vesicles of Kimchi-Derived Lactic Acid Bacteria (Leuconostoc mesenteroides, Latilactobacillus curvatus, and Lactiplantibacillus plantarum)

Abstract

Lactic acid bacteria present in Kimchi, such as Leuconostoc mesenteroides (Lm), Latilactobacillus curvatus (Lc), and Lactiplantibacillus plantarum (Lp) produce extracellular vesicles (ECVs) that modulate immune responses. The ECVs of probiotic Kimchi bacteria are abbreviated as LmV, LcV, and LpV. Treatment of macrophages (RAW264.7) with ECVs (LmV, LcV, and LpV) increased the production of nitric oxide (NO), tumor necrosis factor (TNF)-α, and interleukin-6 (IL-6). Immunostimulatory effects exerted on the RAW264.7 cells were stronger after treatments with LmV and LcV than with LpV. Treatment of mice with LcV (1 mg/kg, orally) induced splenocyte proliferation and subsequent production of both NO and cytokines (INF-γ, TNF-α, IL-4, and IL-10). Furthermore, pre-treatment of macrophages and microglial cells with ECVs prior to LPS stimulation significantly attenuated the production of NO and pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6). Therefore, ECVs (LmV, LcV, and LpV) prevent inflammatory responses in the LPS-stimulated microglial cells by blocking the extracellular signal-regulated kinase (Erk) and p38 signaling pathways. These results showed that LmV, LcV, and LpV from Kimchi probiotic bacteria safely exert immunomodulatory effects.

Lactic Acid Bacteria (LAB) and Neuroprotection, What Is New? An Up-To-Date Systematic Review

“…EVs from Leuconostoc mesenteroides, Latilactobacillus curvatus , and Lactiplantibacillus plantarum significantly inhibited the production of NO and pro-inflammatory cytokine by LPS-stimulated microglia cells with neuroinflammation. This inhibitory effect is associated with the suppression of the MAPK signaling pathways through phosphorylation of p38 and ERK [ 52 ].…”

“…LAB also exerts immunostimulatory effects as demonstrated in macrophage cells and T-lymphocytes isolated from the spleen of mice [ 52 ]. Tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and nuclear factor-kappa B (NF-KB) are proteins that are directly involved in neuroinflammatory processes and the activation of microglia [ 73 ].…”

“…A crucial component of the neuroinflammatory system set off by glial cells during the onset of neurodegenerative disorders is the MAP-ERK pathway [ 85 ]. EVs derived from LAB ( Leuconostoc mesenteroides , Latilactobacillus curvatus , and Lactiplantibacillus plantarum ) demonstrated anti-inflammatory activity on microglial cells, mediated by effects on p38 and ERK signaling pathways [ 52 ]. Pretreatment of LAB-derived EVs prior to LPS induction has significantly decreased the activation of phosphorylated ERK and p38 protein in comparison to control LPS-treated microglial cells [ 52 ].…”

High performance anion exchange chromatography purification of probiotic bacterial extracellular vesicles enhances purity and anti‐inflammatory efficacy

“…To enable iterative development of our purification method in a high throughput fashion, we utilized the mouse macrophage cell line RAW264.7. The RAW264.7 cell line has previously been validated to recapitulate in vivo anti‐inflammatory responses of EVs, and for study of in vitro anti‐inflammatory bioactivity of BEVs (Hu et al, 2020; Kim et al, 2022; Pacienza et al, 2019). In L. casei AEC elution fractions, we observed high particle counts (Figure 2d), presence of BEVs in electron micrographs (Figure 2e), and anti‐inflammatory bioactivity (Figure 2f), altogether indicating that AEC can separate L. casei BEVs.…”

Extracellular Vesicles as Novel Drug-Delivery Systems through Intracellular Communications

“…It is thought that there is a mechanism by which molecules with immunomodulatory ability are secreted from microorganisms that have beneficial effects to the outside of the cell and delivered to the target cell of the living body [131]. When various EVs derived from bifizus, butyric-acid, and lactic-acid bacteria were added to two types of immune cells, mouse macrophage-like-cell line RAW264.7 and dendritic-cell line DC2.4, the production of inflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) was increased [132][133][134][135]. This report confirmed that EVs derived from probiotics have immunostimulatory abilities.…”