Extracellular vesicles derived from Trichinella spiralis prevent colitis by inhibiting M1 macrophage polarization.

ABSTRACT

Extracellular vesicles (EVs) are membranous containers released by cells that are powerful agents of intercellular communication. EVs have been described for various parasites and are associated with tissue inflammation. Several studies have demonstrated that parasite EVs can have either pro- or anti-inflammatory impacts, depending on the type of parasite. To evaluate the immunomodulatory properties of EVs produced by Trichinella spiralis (T. spiralis), we established a mouse model with dextran sulphate sodium (DSS)-induced colitis. The muscle larvae of T. spiralis were cultured in vitro and the released EVs were isolated by ultracentrifugation. T. spiralis EVs (Ts-EVs) were characterized according to morphology, size and constituent surface proteins (CD63, Enolase and Hsp70). Mice were treated with water containing 3% DSS after last intraperitoneal injection of Ts-EVs. Disease activity index (DAI), macroscopic and histopathological scores of Ts-EVs group was lower than DSS group. And Ts-EVs prevented the increase in the expression of TNF-α, IFN-γ, IL-17A and IL-1ß observed in the colon of DSS-treated mice. In contrast, upregulation of IL-4, IL-10, TGF-ß and IL-13 expression was detected in Ts-EVs+DSS group. In addition, Ts-EVs increased the infiltration of alternatively activated (M2) macrophages into the colon. The expression of CD206 (M2 marker) in the mesenteric lymph nodes (MLN) of mice with colitis increased in Ts-EVs+DSS group. Furthermore, Ts-EVs interfered with both the NF-κB and MAPK signalling pathways. Taken together, our findings demonstrate that Ts-EVs can affect the development of inflammation in DSS-induced colitis by inhibiting M1 macrophage polarization, due to their immunomodulatory ability.