Extracellular vesicles derived from specific lactic acid bacteria have agonistic activity against formyl peptide receptor 2

Abstract

Lactic acid bacteria (LAB) play important roles in food microbiology and human health. Extracellular vesicles (EVs), which are drug transporters that contain functional components, derived from LAB have been recognized as materials with various beneficial effects, such as their anti-inflammatory effects. Owing to the complexity arising from strain-dependent functional differences in LAB, the functions of EVs derived from LAB have not been well elucidated. To investigate the strain-specific functions of EVs from LAB, we evaluated the ability of EVs from different LAB to induce interleukin 10 (IL-10) secretion by M2-like macrophages. The use of EVs with an increased capacity to induce IL-10 secretion and a G protein-coupled receptor (GPCR) assay revealed that EVs derived from specific lactic acid bacterial strains have agonistic effects against formyl peptide receptor 2 (FPR2). A strong and significant correlation between the ability of EVs derived from LAB to induce IL-10 secretion and agonistic activity against FPR2 was identified, and treatment with an FPR2 antagonist reduced the secretion of IL-10 induced by EVs from a specific lactic acid bacterial strain. Ultraviolet B (UVB) irradiation-induced damage to human keratinocytes was reversed after treatment with EVs with agonistic activity against FPR2, and this restorative effect was abolished by treatment with an FPR2 antagonist. In this study, we demonstrate for the first time that EVs derived from specific LAB have agonistic activity against FPR2; this activity could be a crucial factor in the anti-inflammatory effects of EVs released from specific LAB.

Keywords: Agonist; Anti-inflammatory; Extracellular vesicles; Formyl peptide receptor 2; Lactic acid bacteria.