Exosomes are membrane-bound structures released by cells into the external environment that carry a significant amount of important cargo, such as proteins, DNA, RNA, and lipids. They play a crucial role in intercellular communication. Parasites have complex life cycles and can release exosomes at different stages. Exosomes released by parasitic pathogens or infected cells contain parasitic nucleic acids, antigenic molecules, virulence factors, drug-resistant proteins, proteases, lipids, etc. These components can regulate host gene expression across species or modulate signaling pathways, thereby dampening or activating host immune responses, causing pathological damage, and participating in disease progression. This review focuses on the means by which parasitic exosomes modulate host immune responses, elaborates on the pathogenic mechanisms of parasites, clarifies the interactions between parasites and hosts, and provides a theoretical basis and research directions for the prevention and treatment of parasitic diseases.

Schistosomiasis, a parasite infectious disease caused by Schistosoma japonicum, often leads to egg granuloma and fibrosis due to the inflammatory reaction triggered by egg antigens released in the host liver. This study focuses on the role of the egg antigens CP1412 protein of S. japonicum (SjCP1412) with RNase activity in promoting liver fibrosis. In this study, the recombinant egg ribonuclease SjCP1412, which had RNase activity, was successfully prepared. By analysing the serum of the population, it has been proven that the anti-SjCP1412 IgG in the serum of patients with advanced schistosomiasis was moderately correlated with liver fibrosis, and SjCP1412 may be an important antigen associated with liver fibrosis in schistosomiasis. In vitro, the rSjCP1412 protein induced the human liver cancer cell line Hep G2 and liver sinusoidal endothelial cells apoptosis and necrosis and the release of proinflammatory damage-associated molecular patterns (DAMPs). In mice infected with schistosomes, rSjCP1412 immunization or antibody neutralization of SjCP1412 activity significantly reduced cell apoptosis and necroptosis in liver tissue, thereby reducing inflammation and liver fibrosis. In summary, the SjCP1412 protein plays a crucial role in promoting liver fibrosis during schistosomiasis through mediating the liver cells apoptosis and necroptosis to release DAMPs inducing an inflammatory reaction. Blocking SjCP1412 activity could inhibit its proapoptotic and necrotic effects and alleviate hepatic fibrosis. These findings suggest that SjCP1412 may be served as a promising drug target for managing liver fibrosis in schistosomiasis japonica.

Schistosomiasis is an immunopathogenic disease characterized by egg granuloma and fibrosis. The hepatic fibrosis of schistosomiasis is caused by the coordinated action of local immune cells, liver-resident cells and related cytokines around the eggs of the liver. B-cell-activating factor (BAFF), expressed in many cells, is an essential factor for promoting the survival, differentiation, and maturation of cells. The overexpression of BAFF is closely related to many autoimmune diseases and fibrosis, but has not been reported to play a role in liver fibrosis caused by schistosomiasis. In the study, we found that, during Schistosoma japonicum (S. japonicum) infection in mice, the level of BAFF and its receptor BAFF-R progressively increased, then decreased with the extension of infection time, which was consistent with the progression of hepatic granuloma and fibrosis. Anti-BAFF treatment attenuated the histopathological damage in the liver of infected mice. The average areas of individual granulomas and liver fibrosis in anti-BAFF treatment mice were significantly lower than those in control mice, respectively. Anti-BAFF treatment increased the IL-10, decreased IL-4, IL-6, IL-17A, TGF-β, and downregulated the antibody level against S. japonicum antigens. These results suggested that BAFF acts a strong player in the immunopathology of schistosomiasis. Anti-BAFF treatment may influence Th2 and Th17 responses, and reduce the inflammatory reaction and fibrosis of schistosomiasis liver egg granuloma. It is suggested that BAFF might be a prospective target for the development of new methods to treat schistosomiasis liver fibrosis.

Schistosomiasis is a parasitic disease that poses a serious threat to human health. However, the pathogenic mechanism during the progression of Schistosoma japonicum infection remains unclear. In order to elucidate this mechanism, we used single-cell RNA sequencing (scRNA-seq) to investigate the transcriptome characteristics of the cellular (single-cell) landscape in the livers of mice infected with Schistosoma japonicum, which were divided into three groups: uninfected mice (0 week (w)), infected mice at 6 w post-infection (the acute phase), and infected mice at 10 w post-infection (the chronic phase). A total of 31,847 liver cells were included and clustered into 21 groups. The cells and T-cells had high heterogeneity in the liver during the progression of schistosome infection. The number and intensity of the intercellular interactions significantly increased at 6 w after infection but decreased at 10 w. The inflammatory signaling pathways chemoattractant cytokine ligand (CCL)5-chemokine C-C-motif receptor (CCR)5 between macrophages and T-cells were predominant at 6 w post-infection; the CCL6-CCR2 signaling pathway between macrophages was predominant at 10 w. The CD80 signaling pathway related to T-cell activation was increased at 6 w after infection, and increased expression of its receptor CD28 on the surfaces of CD4⁺ and CD8⁺ T-cells was confirmed by flow cytometry, suggesting an increase in their activation. In addition, scRNA-seq and quantitative reverse transcription polymerase chain reaction (qRT-PCR) confirmed that the intercellular communication between secretory phosphoprotein 1 (SPP1)-cluster of differentiation (CD44), insulin-like growth factor (IGF)-1-IGF1r and visfatin-insulin receptor (Insr) associated with bone metabolism and insulin metabolism was increased and enhanced in the liver at 6 w post-infection. Overall, we provide the comprehensive single-cell transcriptome landscape of the liver in mice during the progression of schistosome infection and delineate the key cellular and molecular events involved in schistosome infection-induced liver injury and fibrosis. The elevated CCL5-CCR5 and CCL6-CCR2 signaling pathways in the liver may be a drug target for liver injury and fibrosis caused by schistosome infection, respectively.

Schistosomiasis, a zoonotic parasitic disease caused by schistosome infection, remains a serious public health concern. However, diagnostic methods with both high sensitivity and specificity or early diagnosis for detecting schistosome infection are still lacking. This study aimed to evaluate the diagnostic potential of parasite-derived exosomes miRNAs in Schistosoma japonicum ( S. japonicum ) infection. Exosomes were isolated and purified from adult worms and eggs of S. japonicum using ultracentrifugation. Nine highly abundant miRNAs were identified in these exosomes through small RNA sequencing. TaqMan probe-based reverse transcription real-time PCR (RT-qPCR) revealed that serum levels of all nine parasite-derived miRNAs were significantly elevated in infected mice at different time points post-infection. Compared with healthy controls, infected patients exhibited significantly elevated serum levels of sja-miR-61 and sja-miR-7-5p. Receiver operating characteristic (ROC) analysis indicated that the area under the curve (AUC) values for serum sja-miR-61 and sja-miR-7-5p were 0.8750 and 0.8375, respectively, surpassing those of the other miRNAs examined in human serum. The sensitivity and specificity for detecting these miRNAs in human serum were 85.00% and 85.00% for sja-miR-61, and 70.00% and 80.00% for sja-miR-7-5p. When both miRNAs were detected in combination, sensitivity increased to 95.00% with a specificity of 75.00%. In mice, the sensitivity and specificity for detecting sja-miR-7-5p at 2 weeks post-infection were 73.33% and 86.67%, improving to 93.33% and 93.33% at 6 weeks. For sja-miR-61, sensitivity and specificity were 93.33% and 80.00% at 2 weeks, reaching 100.00% and 100.00% at 6 weeks. Serum levels of sja-miR-61 and sja-miR-7-5p dropped to undetectable levels two weeks after praziquantel treatment, underscoring their utility in monitoring treatment response. Furthermore, measurement of sja-miR-61 and sja-miR-7-5p in mice with varying infection intensities showed rising serum levels corresponding to increased worm burdens, with a minimum detection threshold equivalent to an infection with 5 cercariae, highlighting the high sensitivity of this approach for detecting low-level infections in mice. Collectively, the detection of these miRNAs in patient or mouse serum using TaqMan RT-qPCR exhibits good sensitivity and specificity, along with considerable value for early diagnosis and treatment monitoring. sja-miR-61 and sja-miR-7-5p represent promising biomarkers for the diagnosis of schistosomiasis japonica.

To further investigate the role of PKCλ/ι in Schistosoma japonicum-induced hepatic fibrosis, we employed a CD4⁺ T-cell-specific PKCλ/ι conditional knockout (KOSJ) mouse model, with wild-type (WTSJ) mice used as controls. Transcriptomic profiling of hepatic mRNA was used to reveal the immune regulatory mechanisms underlying the role of PKCλ/ι in the hepatic fibrosis caused by S. japonicum infection. Flow cytometry, RT–qPCR and ELISA were used to analyze the effects of PKCλ/ι on Tfh and Tfr cells, and single-cell RNA sequencing was used to elucidate the interactions between Tfr and B cells. The results showed that PKCλ/ι deficiency led to altered BCR signaling gene expression, reduced germinal center activity, and decreased anti-SEA antibody levels. Tfh cells and key factors including IL-21, CXCR5, and ICOS were downregulated, while Tfr cells and IL-10⁺ B cells increased. Additionally, hepatic neutrophils decreased and Treg/Tfr ratios rose, with enhanced IL-10-mediated cellular crosstalk. These findings indicate that PKCλ/ι deficiency attenuates liver fibrosis by inhibiting Tfh differentiation, promoting Tfr function, and activating IL-10-producing Breg cells, suggesting its potential as a therapeutic target.