Extracellular vesicles from the trematodes Fasciola hepatica and Dicrocoelium dendriticum trigger different responses in human THP‐1 macrophages. Issue 4 (19th April 2023)

• Record Type: Journal Article
• Authors: Sánchez‐López, Christian M.; González‐Arce, Aránzazu; Soler, Carla; Ramírez‐Toledo, Víctor; Trelis, María; Bernal, Dolores; Marcilla, Antonio
• Is Part Of: Journal of extracellular vesicles. Volume 12:Issue 4(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2023-04-19
• Subjects: Dicrocoelium dendriticum -- Fasciola hepatica -- helminth EVs -- macrophage activation -- monocyte migration -- SEC isolation; Cells -- Mechanical properties -- Periodicals; Transport Vesicles; Cells -- Mechanical properties; Periodicals; Fulltext; Internet Resources; Periodicals; Electronic journals; Periodicals; 571.63
• DOI: 10.1002/jev2.12317
• Languages: English
• ISSNs: 2001-3078

Abstract

Abstract: Extracellular vesicles (EVs) released by the helminths Dicrocoelium dendriticum and Fasciola hepatica are important modulators of the host immune response, contributing to the establishment of the infection. Monocytes and, in particular, macrophages are major regulators of the inflammatory response and are likely responsible for the phagocytosis of most of the parasite EVs. In this study, we isolated EVs from F. hepatica ( Fh EVs) and D. dendriticum ( Dd EVs) by size exclusion chromatography (SEC) and characterized them by nanoparticle tracking analysis, transmission electron microscopy and LC‐MS/MS, and analyzed the cohort of proteins. The treatment of monocytes/macrophages with Fh EVs, Dd EVs or EV‐depleted fractions from SEC, demonstrated species‐specific effects of the EVs. In particular, Fh EVs reduce the migratory capacity of monocytes and the analysis of the cytokine profile showed that they induce a mixed M1/M2 response, exerting anti‐inflammatory properties in Lipopolysaccharide‐activated macrophages. In contrast, Dd EVs do not affect monocyte migration and seem to have pro‐inflammatory properties. These results correlate with the differences in the life cycle of both parasites, suggesting different host immune responses. Only F. hepatica migrates to the bile duct through the liver parenchyma, driving the host immune response to heal deep erosions. Furthermore, the proteomic analysis of the macrophages upon Fh EV treatment identified several proteins that might be involved in Fh EV‐macrophage interactions.