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)-alpha, 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-gamma, TNF-alpha, 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-alpha, IL-1 beta, 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.