Background: Epidemiologic studies and animal model experiments have shown that parasites have significant modulatory effects on autoimmune disorders, including inflammatory bowel disease (IBD). Recombinant Sj16 (rSj16), a 16-kDa secreted protein of Schistosoma japonicum (S.japonicum) produced by Escherichia coli (E. coli), has been shown to have immunoregulatory effects in vivo and in vitro. In this study, we aimed to determine the effects of rSj16 on dextran sulfate sodium (DSS)-induced colitis.Methods: DSS-induced colitis mice were treated with rSj16. Body weight loss, disease activity index (DAI), myeloperoxidase (MPO) activity levels, colon lengths, macroscopic scores, histopathology findings, inflammatory cytokine levels and regulatory T cell (Treg) subset levels were examined. Moreover, the differential genes expression after treated with rSj16 were sequenced, analyzed and identified.Results: rSj16 attenuated clinical activity of DSS-induced colitis mice, diminished pro-inflammatory cytokine production, up-regulated immunoregulatory cytokine production and increased Treg percentages in DSS-induced colitis mice. Moreover, DSS-induced colitis mice treated with rSj16 displayed changes in the expression levels of specific genes in the colon and show the crucial role of peroxisome proliferator activated receptor α (PPAR-α) signaling pathway. PPAR-α activation diminished the therapeutic effects of rSj16 in DSS-induced colitis mice, indicating that the PPAR-α signaling pathway plays a crucial role in DSS-induced colitis development.Conclusions: rSj16 has protective effects on DSS-induced colitis, effects mediated mainly by PPAR-α signaling pathway inhibition. The findings of this study suggest that rSj16 may be useful as a therapeutic agent and that PPAR-α may be a new therapeutic target in the treatment of IBD.

Exosomes are 30–150 nm small membrane vesicles that are released into the extracellular medium via cells that function as a mode of intercellular communication. Dendritic cell (DC)-derived exosomes modulate immune responses and prevent the development of autoimmune diseases. Moreover, Schistosoma japonicum eggs show modulatory effects in a mouse model of colitis. Therefore, we hypothesized that exosomes derived from DCs treated with S. japonicum soluble eggs antigen (SEA; SEA-treated DC exosomes) would be useful for treating inflammatory bowel disease (IBD). Exosomes were purified from the supernatant of DCs treated or untreated with SEA and identified via transmission electron microscopy, western blotting and NanoSight. Acute colitis was induced via the administration of dextran sulfate sodium (DSS) in drinking water (5.0%, wt/vol). Treatment with exosomes was conducted via intraperitoneal injection (i.p.; 50 μg per mouse) from day 0 to day 6. Clinical scores were calculated based on weight loss, stool type, and bleeding. Colon length was measured as an indirect marker of inflammation, and colon macroscopic characteristics were determined. Body weight loss and the disease activity index of DSS-induced colitis mice decreased significantly following treatment with SEA-treated DC exosomes. Moreover, the colon lengths of SEA-treated DC exosomes treated colitis mice improved, and their mean colon macroscopic scores decreased. In addition, histologic examinations and histological scores showed that SEA-treated DC exosomes prevented colon damage in acute DSS-induced colitis mice. These results indicate that SEA-treated DC exosomes attenuate the severity of acute DSS-induced colitis mice more effectively than DC exosomes. The current work suggests that SEA-treated DC exosomes may be useful as a new approach to treat IBD.

Sun (2020) Sja-miR-71a in Schistosome egg-derived extracellular vesicles suppresses liver fibrosis caused by schistosomiasis via targeting semaphorin 4D,

BackgroundAngiostrongylus cantonensis, an important foodborne parasite, can induce serious eosinophilic meningitis in non-permissive hosts, such as mouse and human. However, the characteristics and mechanisms of the infection are still poorly understood. This study sought to determine the key molecules and its underlying mechanism in inducing brain eosinophilic infiltration caused by Angiostrongylus cantonensis.MethodsMathematical models were established for prediction of significantly changing genes and the functional associated protein with RNA-seq data in Angiostrongylus cantonensis infection. The expression level of Chi3l3, the predicted key molecule, was verified using Western blotting and real-time quantitative PCR. Critical cell source of Chi3l3 and its relationship with eosinophils were identified with flow cytometry, immunohistochemistry, and further verified by macrophage depletion using liposomal clodronate. The role of soluble antigens of Angiostrongylus cantonensis in eosinophilic response was identified with mice airway allergy model by intranasal administration of Alternaria alternate. The relationship between Chi3l3 and IL-13 was identified with flow cytometry, Western blotting, and Seahorse Bioscience extracellular flux analyzer.ResultsWe analyzed the skewed cytokine pattern in brains of Angiostrongylus cantonensis-infected mice and found Chi3l3 to be an important molecule, which increased sharply during the infection. The percentage of inflammatory macrophages, the main source of Chi3l3, also increased, in line with eosinophils percentage in the brain. Network analysis and mathematical modeling predirect a functional association between Chi3l3 and IL-13. Further experiments verified that the soluble antigen of Angiostrongylus cantonensis induce brain eosinophilic meningitis via aggravating a positive feedback loop between IL-13 and Chi3l3.ConclusionsWe present evidences in favor of a key role for macrophave-derived Chi3l3 molecule in the infection of Angiostrongylus cantonensis, which aggravates eosinophilic meningitis induced by Angiostrongylus cantonensis via a IL-13-mediated positive feedback loop. These reported results constitute a starting point for future research of angiostrongyliasis pathogenesis and imply that targeting chitinases and chitinase-like-proteins may be clinically beneficial in Angiostrongylus cantonensis-induced eosinophilic meningitis.Electronic supplementary materialThe online version of this article (10.1186/s12974-018-1071-2) contains supplementary material, which is available to authorized users.