Extracellular vesicles from Trichinella spiralis: Proteomic analysis and protective immunity

Abstract

Trichinella spiralis (T. spiralis) derived extracellular vesicles (EVs) have been proposed to play a key role in regulating the host immune responses. In this study, we provided the first investigation of EVs proteomics released by T. spiralis muscle larvae (ML). T. spiralis ML EVs (Ts-ML-EVs) were successfully isolated and characterized by transmission electron microscopy (TEM) and western blotting. Using liquid chromatograph mass spectrometer (LC-MS/MS) analysis, we identified 753 proteins in the Ts-ML-EVs proteome and annotated by gene ontology (GO). These proteins were enriched in different categories by GO, kyoto encyclopedia of genes and genomes (KEGG) and domain analysis. GO enrichment analysis indicated association of protein deglutathionylation, lysosomal lumen and serine-type endopeptidase inhibitor activity with proteins which may be helpful during parasite-host interaction. Moreover, KEGG enrichment analysis revealed involvement of Ts-ML-EVs proteins in other glycan degradation, complement and coagulation cascades, proteasome and various metabolism pathways. In addition, BALB/c mice were immunized by subcutaneous injection of purified Ts-ML-EVs. Ts-ML-EVs group demonstrated a 23.4% reduction in adult worms and a 43.7% reduction in ML after parasite challenge. Cellular and humoral immune responses induced by Ts-ML-EVs were detected, including the levels of specific antibodies (IgG, IgM, IgE, IgG1 and IgG2a) as well as cytokines (IL-12, IFN-γ, IL-4 and IL-10) in serum. The results showed that Ts-ML-EVs could induce a Th1/Th2 mixed immune response with Th2 predominant. This study revealed a potential role of Ts-ML-EVs in T. spiralis biology, particularly in the interaction with host. This work provided a critical step to against T. spiralis infection based on Ts-ML-EVs.

Large-scale proteomic analysis of T. spiralis muscle-stage ESPs identifies a novel upstream motif for in silico prediction of secreted products

“…Given their immunomodulatory effects, MSL EVs must be capable of transporting proteins from the worm to the cell surface where they can interface with the immune system. A recent study that proteomically profiled EVs derived from MSL-stage T. spiralis identified 753 proteins [66]. Of these, 175 were also present in our dataset ( Supplementary Table 1) .…”

Large-scale proteomic analysis of T. spiralis muscle-stage ESPs identifies a novel upstream motif for in silico prediction of secreted products

“…Given their immunomodulatory effects, MSL EVs must be capable of transporting proteins from the worm to the cell surface where they can interface with the immune system. A recent study that proteomically profiled EVs derived from MSL-stage T. spiralis identified 753 proteins (Gao et al, 2022). Of these, 175 were also present in our dataset (Supplementary Table 1).…”

Chloroquine induces eryptosis inP. falciparum-infectedred blood cells and the release of extracellular vesicles with a unique protein profile

“…Interestingly, proteasome subunits have been identified in EVs secreted by other protozoa, helminths and ectoparasites (33). For example, in the protozoa Acanthamoeba castellanii the proteasome is involved in the regulation of encystation and extracellular proteolytic activities (34); whereas in Trichinella spiralis the proteasome subunit beta type-7 (PST) has been expressed at different developmental stages and is responsible for a decrease of 45.7% adult worm burden in mice suggesting PST as vaccine antigen against the parasite infection (35). Recently, it has been demonstrated that iRBCs-derived EVs contain functional 20S proteasome complexes (15).…”