Echinococcus Granulosus Infection Research Articles

Association of IL-9 Cytokines with Hepatic Injury in Echinococcus granulosus Infection.

Cystic echinococcosis (CE) is a zoonotic disease caused by the parasite Echinococcus granulosus (E. granulosus), which can lead to the formation of liver lesions. Research indicates that E. granulosus releases both Toll-like receptor 2 (TLR2) and Interleukin-9 (IL-9), which can potentially impair the body's innate immune defenses and compromise the liver's ability to fight against diseases. To investigate the role of TLR2 and IL-9 in liver damage caused by E. granulosus infection, samples were initially collected from individuals diagnosed with CE. Subsequently, BALB/c mice were infected with E. granulosus at multiple time points (4 weeks, 12 weeks, 32 weeks) and the expression levels of these markers was then assessed at each of these phases. Furthermore, a BALB/c mouse model was generated and administered anti-IL-9 antibody via intraperitoneal injection. The subsequent analysis focused on the TLR2/MyD88/NF-κB signaling pathway and the expression of IL-9 in E. granulosus was examined. A co-culture experiment was conducted using mouse mononuclear macrophage cells (RAW264.7) and hepatic stellate cells (HSCs) in the presence of E. granulosus Protein (EgP). The findings indicated elevated levels of IL-9 and TLR2 in patients with CE, with the activation of the signaling pathway significantly increased as the duration of infection progressed. Administration of anti-IL-9 in mice reduced the activation of the TLR2/MyD88/NF-κB signaling pathway, exacerbating liver injury. Moreover, EgP stimulates the TLR2/MyD88/NF-κB signaling pathway, resulting in the synthesis of α-SMA and Collagen I. The data suggest that infection with E. granulosus may stimulate the production of IL-9 through the activation of the TLR2/MyD88/NF-κB signaling pathway, which is mediated by TLR2. This activation stimulates RAW264.7 and HSCs, exacerbating liver injury and fibrosis.

Hepatic Hydatid cyst in children: An experience from East of Turkey

İntoduction: Hydatid cyst is a parasitic disease caused by the infection of Echinococcus granulosus and rarely Echinococcus alveolaris eggs, which are endemic in our country. Current treatment options for liver hydatid cysts; They can be listed as medical treatment, surgical treatment, percutaneous drainage and clinical follow-up only. In this study, the effectiveness of the WHO-IWGE protocol in terms of diagnosis and treatment strategies in our pediatric cases of liver hydatid cyst in a health institution in eastern Turkey was evaluated in the light of the literature. Material Method: Pediatric patients between the ages of 0-16 who were diagnosed with KcKH and followed up and treated were evaluated retrospectively. In pre-operative evaluation, lung radiography, abdominal ultrasonography, serological tests, hemogram and liver function tests were routinely performed. Results: 250 child patients between the ages of 0 and 16, whose data were fully available, were included in the study. 118 of the cases were girls and 132 were boys. The average age was 11.2 years. Most of the KcKH patients were admitted to the hospital for another reason and the cyst was detected incidentally. Of the 65 patients requiring surgery, 17 were patients who initially underwent primary intervention with PAIR. Patients who underwent PAIR were observed for one night and discharged in an average of 18 hours. Patients with free drainage were discharged in 2-4 days. The average length of stay for patients who underwent open surgery was found to be 9 days. In conclusion; The Gharbi classification updated by WHO is effective and reliable in determining the KcKH treatment strategy. In cases who are receiving chemotherapy and an intervention decision is made, a final USG is performed just before the procedure; It can provide both a change in treatment management and more patients benefiting from medical treatment.

Effects of Dihydroartemisinin against Cystic Echinococcosis In Vitro and In Vivo.

Cystic echinococcosis (CE) is a disease caused by the infection of Echinococcus granulosus. We sought to investigate the effects of dihydroartemisinin (DHA) against CE under in vitro and in vivo conditions. Protoscoleces (PSCs) from E. granulosus were divided into control, DMSO, ABZ, DHA-L, DHA-M, and DHA-H groups. PSC viability after DHA treatment was determined based on the eosin dye exclusion test, alkaline phosphatase content detection, and ultrastructure observation. DNA oxidative damage inducer hydrogen peroxide (H2O2), reactive oxygen species (ROS) scavenger mannitol, and the DNA damage repair inhibitor velparib were used to explore the anti-CE mechanism of DHA. The anti-CE effects and CE-induced liver injury and oxidative stress of DHA at different doses (50, 100, and 200 mg/kg) were assessed in CE mice. DHA showed antiparasitic effects on CE in both in vivo and in vitro experiments. DHA could elevate the ROS level and induce oxidative DNA damage in PSCs, thereby destroying hydatid cysts. DHA could inhibit the growth of cysts in a dose-dependent manner and reduce the content of biochemical parameters associated with liver injury in CE mice. It also significantly reversed oxidative stress in CE mice, which was characterized as the decreased tumor necrosis factor alpha and H2O2 content, as well as the increase of the ratio of glutathione/oxidized glutathione and total superoxide dismutase content. DHA showed antiparasitic effects. DNA damages induced by oxidative stress played important roles in this process.

The mouse model of chronic asthma: Airway remodelling and disease exacerbation by somatic antigen of Echinococcus granulosus.

There is now sufficient evidence to support an inverse association between helminth infection and secreted products with allergic/autoimmune disorders. Accordingly, several experimental studies have shown that Echinococcus granulosus infection and hydatid cyst compounds are able to suppress immune responses in allergic airway inflammation. This is the first study on effects of somatic antigens of E. granulosus on chronic allergic airway inflammation in BALB/c mice. Mice in OVA group were intraperitoneally (IP) sensitized with OVA/Alum. Subsequently, were challenged by nebulizing of OVA 1%. The treatment groups received somatic antigens of protoscoleces on the specified days. Mice in PBS group were received PBS in both sensitization and challenge. The effects of somatic products on development of chronic allergic airway inflammation were evaluated by examining histopathological changes, the recruitment of inflammatory cells in the bronchoalveolar lavage, cytokines production in the homogenized lung tissue, and total antioxidant capacity in serum. Our findings show that the co-administration of somatic antigens of protoscoleces simultaneously with the development of asthma intensifies allergic airway inflammation. The identification of effective components involved in exacerbation of allergic airway inflammation manifestations will be a crucial approach to understanding the mechanism of these interactions.

Notch signaling pathway involved in Echinococcus granulosus infection regulates dendritic cell development and differentiation.

The Notch signaling pathway is involved in the development of many diseases; it regulates the development of dendritic cells (DCs), and affects the immune response of DC-mediated T cells. We previously found that ferritin and malate dehydrogenase (mMDH) in Echinococcus granulosus (E.granulosus) induced different immune responses through sensitized DCs. Therefore, in the study we explored whether the Notch signaling pathway affects the development and differentiation of DCs, causing changes in the immune response of DCs sensitized with E. granulosus antigens, and clarified whether it is involved in E.granulosus infection. We used the Notch signaling pathway inhibitor [N-[3,5-difluorophenace-tyl] -L-alanyl]-S-phenylglycinet-butyl ester (DAPT) or activator Jagged1 to construct in vitro cell models with blocked or activated Notch signaling respectively. We analyzed the effect of Notch signaling on the development and differentiation of DCs by detecting their morphology, migration function, capacity to promote T cell proliferation, and cytokine secretion. We observed the changes in DC response to E. granulosus antigens and the mediated immune response. DAPT inhibited the development and maturation of DCs, which were in a non-responsive or incompetent state, reduced the sensitization of DCs to Eg.ferritin, weakened the migration ability of DCs, disrupted their ability to mediate T-cell proliferation, reduced DC expression of MHCII, CD80, CD60, and CD40 co-stimulatory molecules, prevented the secretion of cytokines and attenuated the expression of Notch1, Notch2, Notch3 receptors, Jagged1, Delta-like 4 (Delta4), and Hes1. Following Jagged1 addition, the function of DCs was restored to some extent, and the expression of Notch1, Delta4 and Hes1 was activated in response to the stimulation of Eg.ferritin. However, Eg.mMDH stimulated DCs to produce an immune response showing weak interference by DAPT and Jagged1. The study suggests that the Notc h signaling pathway is involved in the Eg.ferritin-sensitized DC-mediated immune response, which may become a new target for treating E.granulosus infection.

Precordial pain induced by the isolated cardiac hydatid cyst in interventricular septum: a case report

BackgroundHuman hydatid disease occurs after infection with Echinococcus granulosus, mainly involves liver and lung, while hydatid involves heart is infrequent. A great majority of hydatid diseases could be asymptomatic, and incidentally found through examination. Here, we reported a woman who suffered an isolated cardiac hydatid cyst located at the interventricular septum.Case presentationA 48-year-old woman presented intermittent chest pain was admitted to the hospital. Imaging examination revealed a cyst located at the interventricular septum near the right ventricular apex. Considering medical history, radiological findings and serological results, cardiac hydatid disease was suspected. The cyst was successfully removed, while pathological biopsy confirmed the diagnosis of infection of Echinococcus granulosus. Postoperative course was uneventful, the patient was discharged from hospital without complications.ConclusionFor symptomatic cardiac hydatid cyst, surgical resection is necessary to avoid progression of disease. During surgical procedure, appropriate methods to reduce the potential risk of hydatid cyst metastasis are essential. Besides surgery, combined with regular drug therapy is an effective strategy to prevent reappearance.

Ex vivo Immuno-modulatory effect of Echinococcus granulosus laminated layer during allergic rhinitis and allergic asthma: A study in Algerian Patients

The effect of helminthic infections on allergic diseases and asthma is still inconclusive. Moreover, there is considerable evidence suggesting that nitric oxide (NO), metalloproteinases and pro-inflammatory cytokines play a significant role in the physiopathology of these diseases. In this sense, the aim of our study is to investigate the ex vivo immunomodulatory effect of the laminated layer (LL, outside layer of parasitic cyst) of the helminth Echinococcus granulosus on NO, IL-17A and IL-10 production. In the first step of our study, we evaluated in vivo the NO, MMP-9, IL-17A, IL-10 levels in Algerian patients with allergic asthma and allergic rhinitis and their changes in relation with exacerbation status of the patients. In the principal part of our work, we assessed NO, IL-10 and IL-17A levels in supernatants of patients PBMC cultures before and after stimulation with LL. Our results indicate a significant reduction in NO production by PBMC of patients with allergic rhinitis and allergic asthma whether mild, moderate or severe after stimulation with LL. Interestingly, LL induces a significant decrease in the production of NO and IL17-A levels as well as an increase in the production of IL-10 in the cultures performed with PBMC of patients with severe allergic asthma.Importantly, our data indicate that LL exert a down-modulatory effect on inflammatory mediators (NO, IL-17A) and up immune-regulatory effect on IL-10 production. Collectively, our study supports the hygiene hypothesis suggesting that Echinococcus granulosus infection like other helminths could prevent and/or modulate inflammation responses during inflammatory diseases.

Single-Cell RNA Sequencing Reveals Unique Alterations in the Immune Panorama and Treg Subpopulations in Mice during the Late Stages of Echinococcus granulosus Infection.

Cystic echinococcosis (CE) is a common zoonotic parasitic disease that seriously impacts public health. However, the full spectrum of immune cell changes in Echinococcus granulosus infection, especially the negative immune regulation of subpopulations of regulatory T (Treg) cells, are not yet well understood. In this study, we used single-cell RNA sequencing and immunome repertoire (IR) sequencing to analyze 53,298 cells from the spleens and peripheral blood mononuclear cells (PBMCs) of healthy and E. granulosus-infected mice. We used immunofluorescence combined with RNA fluorescence in situ hybridization and quantitative real-time PCR to verify the sequencing results. Our results showed tissue-specific immune system alterations in mice infected with E. granulosus. E. granulosus-infected mice induced a subpopulation of CD4+ cells with type I interferon production potential. Furthermore, there were six different Treg cell subpopulations in vivo at three stages of differentiation, and Treg subpopulations of different classes and different stages of differentiation showed tissue specificity. After infection, the Lag3hi Treg and Gpr83+Igfbp4+ naive Treg subpopulations were specifically induced in PBMCs and the spleen, respectively. Furthermore, T follicular helper 2 (Tfh2) cells with high expression of Cxxc5 and Spock2 were found in E. granulosus-infected mice. Our data uncovered changes in the full spectrum of immune cells in mice following the late stages of E. granulosus infection, including subpopulations of cells that have not been emphasized in previous studies. These results further enrich the study of the bidirectional immunomodulatory mechanism and offer a different perspective for subsequent studies of infection in E. granulosus.

Hydatid Disease Involving the Entire Femur Treated with Wide Resection and Reconstruction with Total Femur Replacement—a Case Report

Hydatid disease is a rare condition produced most commonly by the infection of Echinococcus granulosus. The disease typically affects the liver and lungs; osseous echinococcosis accounts only for a small portion of the cases. When bone is compromised, treatment can be challenging, and wide resection of infected bone might be needed to avoid recurrence. A 26-year-old man presented with a pathological fracture of his left femur. Imaging and histology studies were consistent with hydatid disease. Due to the extent of the lesion and high risk for recurrence, the treatment consisted of wide surgical excision and total femur replacement prosthesis associated with anthelmintic therapy. The patient completed 2 years of follow-up with no signs of local recurrence. In cases of hydatid disease with extensive involvement of the femur, wide resection and reconstruction with a total femur prosthesis are viable options that could lead to adequate functional results with no recurrence.

The non-oral infection of larval Echinococcus granulosus induces immune and metabolic reprogramming in the colon of mice.

The intestinal tract serves as a critical regulator for nutrient absorption and overall health. However, its involvement in anti-parasitic infection and immunity has been largely neglected, especially when a parasite is not transmitted orally. The present study investigated the colonic histopathology and functional reprogramming in mice with intraperitoneal infection of the larval Echinococcus granulosus (E. granulosus). Compared with the control group, the E. granulosus-infected mice exhibited deteriorated secreted mucus, shortened length, decreased expression of tight junction proteins zonula occludens-1 (ZO-1), and occludin in the colon. Moreover, RNA sequencing was employed to characterize colonic gene expression after infection. In total, 3,019 differentially expressed genes (1,346 upregulated and 1,673 downregulated genes) were identified in the colon of infected mice. KEGG pathway and GO enrichment analysis revealed that differentially expressed genes involved in intestinal immune responses, infectious disease-associated pathways, metabolism, or focal adhesion were significantly enriched. Among these, 18 tight junction-relative genes, 44 immune response-associated genes, and 23 metabolic genes were annotated. Furthermore, mebendazole treatment could reverse the colonic histopathology induced by E. granulosus infection. Intraperitoneal infection with E. granulosus induced the pathological changes and functional reprogramming in the colon of mice, and mebendazole administration alleviated above alternations, highlighting the significance of the colon as a protective barrier against parasitic infection. The findings provide a novel perspective on host-parasite interplay and propose intestine as a possible target for treating parasitic diseases that are not transmitted orally.

A Rare Case of Hepatic MALT Lymphoma with Coexistence of Hepatitis B Virus and Echinococcus Infection

Primary hepatic extranodal mucosa-associated lymphoid tissue (MALT) lymphoma is seen extremely rare compromising 0,016% among non-Hodgkin lymphomas. Association of chronic inflammatory conditions or infectious processes mostly hepatitis B virus (HBV) infection has been reported by scarce number of case presentations. Whereas MALT lymphoma accompanied by echinococcus granulosus infection was described only in one primary pulmonary lymphoma case. We herein present a primary hepatic MALT lymphoma case with both HBV carrier state and liver hydatid cyst history. A 86 years old male patient referred to our clinic with a sole liver mass and was diagnosed with primary hepatic MALT lymphoma by core biopsy. Positron emission tomography detected increased uptake in the liver lesion without any other uptake site. He was successfully treated with rituximab-chemotherapy, tenofovir and albendazole. By adding one more case to the literature we aimed to emphasize the probable etiologic causative role of echinococcus infection in MALT lymphoma.

Coproantigen as a Tool for Monitoring Echinococcus Granulosus Infection in Definitive Host

Coproantigen as a Tool for Monitoring Echinococcus Granulosus Infection in Definitive Host

The single-cell landscape of cystic echinococcosis in different stages provided insights into endothelial and immune cell heterogeneity.

Hydatid cysts and angiogenesis are the key characteristics of cystic echinococcosis, with immune cells and endothelial cells mediating essential roles in disease progression. Recent single-cell analysis studies demonstrated immune cell infiltration after Echinococcus granulosus infection, highlighting the diagnostic and therapeutic potential of targeting certain cell types in the lesion microenvironment. However, more detailed immune mechanisms during different periods of E. granulosus infection were not elucidated. Herein, we characterized immune and endothelial cells from the liver samples of mice in different stages by single-cell RNA sequencing. We profiled the transcriptomes of 45,199 cells from the liver samples of mice at 1, 3, and 6 months after infection (two replicates) and uninfected wild-type mice. The cells were categorized into 26 clusters with four distinct cell types: natural killer (NK)/T cells, B cells, myeloid cells, and endothelial cells. An SPP1+ macrophage subset with immunosuppressive and pro-angiogenic functions was identified in the late infection stage. Single-cell regulatory network inference and clustering (SCENIC) analysis suggested that Cebpe, Runx3, and Rora were the key regulators of the SPP1+ macrophages. Cell communication analysis revealed that the SPP1+ macrophages interacted with endothelial cells and had pro-angiogenic functions. There was an obvious communicative relationship between SPP1+ macrophages and endothelial cells via Vegfa-Vegfr1/Vegfr2, and SPP1+ macrophages interacted with other immune cells via specific ligand-receptor pairs, which might have contributed to their immunosuppressive function. Our comprehensive exploration of the cystic echinococcosis ecosystem and the first discovery of SPP1+ macrophages with infection period specificity provide deeper insights into angiogenesis and the immune evasion mechanisms associated with later stages of infection.

Primary Hydatid Cyst of The Neck: A Rare Presentation

Background: Hydatid cyst of the head and neck region is an uncommon and unique presentation of the disease. Case Report: We hereby present the case of a 26-year-old female who presented with an 8-year history of swelling in the left side of her neck. Imaging and histopathological studies confirmed the swelling to be a hydatid cyst secondary to Echinococcus granulosus infection. Conclusion: A high index of suspicion is required to diagnose hydatid cyst in differential diagnosis of benign swellings of head and neck region.

Study on mechanisms of Th17/Treg imbalance in patients with cystic echinococcosis based on miRNA expression profiles

To investigate the serum microRNA (miRNA) expression and examine the impact of miRNA expression profiles on T helper type 17 (Th17)/regulatory T cells (Treg) imbalance among patients with cystic echinococcosis, so as to provide insights into the illustration of the mechanisms underlying chronic Echinococcus granulosus infections, and long-term pathogenesis. Total RNA was extracted from the sera of cystic echinococcosis patients and healthy controls, and subjected to high-throughput sequencing with the Illumina sequencing platform. Known miRNAs were annotated and new miRNAs were predicted using the miRBase database and the miRDeep2 tool, and differentially expressed miRNAs were identified. The target genes of differentially expressed miRNAs were predicted using the software miRanda and TargetScan, and the intersection was selected for Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Among the differentially expressed miRNAs with the 20 highest fold changes, miRNAs that targeted genes relating to key transcription factors RORC and FOXP3 that determine the production of Th17 and Treg cells or their important regulatory pathways (PI3K-Akt and mTOR pathways) were matched. A total of 53 differentially expressed miRNAs were screened in sera of cystic echinococcosis patients and healthy controls, including 47 up-regulated miRNAs and 6 down-regulated miRNAs. GO enrichment analysis showed that these differentially expressed miRNA were involved DNA transcription and translation, cell components, cell morphology, neurodevelopment and metabolic decomposition, and KEGG pathway analysis showed that the differentially expressed miRNA were mainly involved in MAPK, PI3K-Akt and mTOR signaling pathways. Among the differentially expressed miRNAs with the 20 highest fold changes, there were 3 miRNAs that had a potential for target regulation of RORC, and 15 miRNAs that had a potential to target the PI3K-Akt and mTOR signaling pathways. Significant changes are found in serum miRNA expression profiles among patients with E. granulosus infections, and differentially expressed miRNAs may lead to Th17/Treg imbalance through targeting the key transcription factors of Th17/Treg or PI3K-Akt and mTOR pathways, which facilitates the long-term parasitism of E. granulosus in hosts and causes a chronic disease.

Risk Factors Associated With Echinococcosis in the General Chinese Population: A Meta-Analysis and Systematic Review.

BackgroundEchinococcosis is a severe zoonotic disease that imposes a substantial burden on human life. This meta-analysis aimed to summarize available data on the prevalence of human echinococcosis and identify the key risk factors for echinococcosis in the Chinese general population.MethodsRelevant studies were comprehensively searched in the PubMed, EMBASE, Web of Science, Cochrane, Chinese National Knowledge Infrastructure (CNKI), Chongqing VIP Information (VIP), Wanfang and SinoMed databases until August 22, 2020. A random-effects model was used to estimate the pooled odds ratio (OR) and 95% confidence interval (95% CI). The I2 and Q statistics were calculated to evaluate the heterogeneity, and potential sources of heterogeneity were identified using sensitivity analysis and subgroup analysis. Publication bias was estimated by funnel plots and Egger's test.ResultsA total of 1026 studies were identified through the database search, of which 26 were eligible for this meta-analysis. The pooled prevalence of AE and CE were 2.88% and 5.66%, respectively. Ethnicity (OR = 2.93, 95% CI: 1.81–4.75; I2 = 0), herdsman occupation (OR = 2.66, 95% CI: 2.25–3.14; I2 = 8.0%), not washing hands before meals (OR = 2.40, 95% CI: 1.34–4.28; I2 = 82.8%) and being female (OR = 1.45, 95% CI: 1.26–1.66; I2 = 33.9%) were risk factors for AE. The top five risk factors for CE were ethnicity (OR = 3.18, 95% CI: 1.55–6.52; I2 = 79.2%), nomadism (OR = 2.71, 95% CI: 1.65–4.47; I2 = 55.8%), drinking nonboiled water (OR = 2.47, 95% CI: 1.36–4.47; I2 = 85.7), feeding viscera to dogs (OR = 2.35, 95% CI: 1.89–2.91; I2 = 21.5%), and herdsman occupation (OR = 2.19, 95% CI: 1.67–2.86; I2 = 85.1%).ConclusionsThis study generalized articles that have contributed to our current understanding of the epidemic of human echinococcosis (AE and CE) in China over the years. The results support that the ethnicity and dog-related factors are major risk factors for both CE and AE. The identification of echinococcosis risk factors may aid researchers and policymakers in improving surveillance and preventive measures aimed at reducing Echinococcus granulosus and Echinococcus multilocularis infection in humans.

Expression profiling of exosomal miRNAs derived from different stages of infection in mice infected with Echinococcus granulosus protoscoleces using high-throughput sequencing.

Echinococcosis is a worldwide zoonosis. The mechanism of the establishment, growth, and persistence of parasites in the host has not been fully understood. Exosomes are found to be a way of information exchange between parasites and hosts. They exist in various body fluids widely. There are few studies on host-derived exosomes and their miRNA expression profiles at different infection time points. In this study, BALB/c mice were intraperitoneally infected with protricercariae. Exosomes were extracted from plasma (0, 3, 9, and 20weeks post infection), and the expression profiles of exosome miRNA in the peripheral blood of mice were determined using RNA-sequencing. Compared to the 0week groups, 24, 35, and 22 differentially expressed miRNAs were detected in infected mouse at the three infection stages, respectively. The results showed that there were significant differences in the miRNAs of exosomes at different infection time points. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to annotate the different miRNAs. The results showed that the biological pathways of parasites changed significantly at different stages of infection, with many significant and abundant pathways involved in cell differentiation, inflammation, and immune response, such as MAPK signaling pathway, Th17 cell differentiation, Wnt signaling pathway, FoxO signaling pathway, Notch signaling pathway, etc. These results suggest that miRNA may be an important regulator of interactions between Echinococcus granulosus and host. The data provided here provide valuable information to increase understanding of the regulatory function of microRNAs in the host microenvironment and the mechanism of host-parasite interaction. This may help us to find targets for Echinococcus granulosus to escape host immune attack and control Echinococcus granulosus infection in the future.

Transcriptomic Profiles of Splenic CD19+ B Cells in Mice Chronically Infected With the Larval Echinococcus granulosus.

BackgroundWe previously reported that the larval Echinococcus granulosus (E. granulosus) infection can expand the population of regulatory B cells in mice, thereby inhibiting the anti-infective immunity. However, the underlying mechanism is still largely unknown. This study further investigated the holistic transcriptomic profiles of total splenic B cells following the chronic infection of the parasite.MethodsThe infection model of larval E. granulosus was established by intraperitoneal inoculation with 2000 protoscolexes. Magnetic-Activated Cell Separation (MACS) was used to isolate the total splenic B cells. RNA sequencing was performed to screen the differentially expressed genes (DEGs) after infection. The expression of selected DEGs was verified using qRT-PCR. Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and Co-expression network analysis were applied to predict these DEGs' underlying biological processes, pathways, and interactions respectively.ResultsA total of 413 DEGs were identified in larval E. granulosus infected B cells, including 303 up- and 110 down-regulated genes. Notably, most DEGs related to inflammation and chemotaxis were significantly upregulated after infection. In line with these changes, significant expression upregulation of DEGs associated with fatty acid oxidation, lipid synthesis, lipolysis, lipid transport, and cholesterol biosynthesis, were observed in infected B cells. Co-expression network analysis showed an intimate interaction between these DEGs associated with immune and metabolism.ConclusionsThe present study revealed that the larval E. granulosus infection induces metabolic reprogramming of B cells, which provides a novel clue to clarify the immunoregulatory mechanism of B cells in parasitic infection.

Role of inducible costimulatory molecules (ICOS) and related cytokines in immune regulation of Echinococcus granulosus infections in mice

To investigate the roles of inducible costimulatory molecules (ICOS) and related cytokines in the immune regulation of Echinococcus granulosus infections in mice. Eighty BALB/c mice (weight 18-22 g) were divided into the control and infection groups, of 40 animals in each group. E. granulosus infection was modeled in mice by intraperitoneal injection of 10 000 protoscoleces per mouse. Serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) and peripheral interleukin-4 (IL-4) and IL-10 levels were measured 2, 8, 30, 60, 180 days post-infection. Mouse liver specimens were excised for hematoxylin-eosin (HE) staining and immunostaining, and ICOS expression was quantified in mouse liver specimens using quantitative real-time PCR (qPCR) assay. There were no significant differences in serum ALT (F = 12.082, P < 0.05), AST (F = 6.347, P < 0.05) or ALP levels (F = 52.186, P < 0.05) in mice 2, 8, 30, 60 and 180 days post-infection with E. granulosus. The serum ALT levels were significantly higher in the infection group than in the control group 2 [(61.72 ± 9.89) vs. (50.65 ± 4.67)U/L, P < 0.05] and 30 days post-infection [(80.61 ± 23.71)vs.(67.75 ± 9.79)U/L, P < 0.05], and the serum ALT levels were significantly higher in the infection group than in the control group 2 [(181.06 ± 60.61) vs.(115.58 ± 17.66)U/L, P < 0.05] and 180 days post-infection [(137.84 ± 29.01) vs. (108.05 ± 10.33) U/L, P < 0.05], while greater serum ALP levels were measured in the infection group than in the control group 2 [(162.90 ± 21.04)vs.(64.54 ± 5.99)U/L, P < 0.05], 8[(176.36 ± 24.56) vs. (62.70 ± 9.21)U/L, P < 0.05] and 30 days post-infection [(138.86 ± 13.59) vs. (58.60 ± 5.28) U/L, P < 0.05]. A few inflammatory cells were seen in mouse liver in the infection group 30 days post-infection, and no apparent changes were found in the mouse hepatic structure 60 days post-infection. On day 180 post-infection, a large number of epithelium-like cells presented fibrotic growth in mouse liver in the cyst-infiltrating regions, with cuticula formation seen, and plenty of red cells were present in lesions and hepatocyte space. Positive ICOS expression was detected in mouse liver in the infection group, with ICOS-positive cells predominantly seen in the cytoplasm of the hepatocyte, and the ICOS expression increased over time. The relative ICOS mRNA expression was 2.732 ± 0.094 on day 180 post-infection, which was significantly greater than that on day 2 postinfection (0.746 ± 0.049). There were no significant differences in serum IL-4 or IL-10 levels at different time points after E. granulosus infections, while the serum IL-4 and IL-10 levels peaked in the infection group 180 days and 60 days post-infection, respectively. Higher serum IL-4 levels were measured in the infection group than in the control group 8 [(22.50 ± 3.24) vs. (5.82 ± 0.49) pg/mL, P < 0.05], 30 [(15.49 ± 4.73) vs. (5.10 ± 1.38) pg/mL, P < 0.05], 60 [(36.93 ± 6.14) vs. (4.13 ± 1.19) pg/mL, P < 0.05] and 180 days post-infection [(198.35 ± 0.70) vs. (4.19 ± 0.98) pg/mL, P < 0.05], and higher IL-10 levels were measured in the infection group than in the control group 2 [(4.84 ± 1.91) vs. (2.11 ± 1.03) pg/mL, P < 0.05], 8 [(44.72 ± 14.63) vs. (3.16 ± 0.60) pg/mL, P < 0.05], 30 [(25.47 ± 8.00) vs. (3.83 ± 1.87) pg/mL, P < 0.05], 60 [(187.16 ± 60.44) vs. (3.69 ± 1.05) pg/mL, P < 0.05] and 180 days post-infection [(85.40 ± 7.15) vs. (3.25 ± 0.93) pg/mL, P < 0.05]. High ICOS expression is present in the liver of mice with E. granulosus infections. The positive ICOS expression and immune activation levels increase with the time of E. granulosus infections, leading to aggravation of hepatocyte injury caused by inflammation.

Exacerbation of allergic asthma by somatic antigen of Echinococcus granulosus in allergic airway inflammation in BALB/c mice

BackgroundThere is ample evidence demonstrating a reverse relationship between helminth infection and immune-mediated diseases. Accordingly, several studies have shown that Echinococcus granulosus infection and hydatid cyst compounds are able to suppress immune responses in allergic airway inflammation. Previous studies have documented the ability of hydatid cysts to suppress aberrant Th2 immune response in a mouse model of allergic asthma. However, there is a paucity of research on the effects of protoscoleces on allergic asthma. Thus, this study was designed to evaluate the effects of somatic antigens of protoscoleces in a murine model of allergic airway inflammation.MethodsOvalbumin (OVA)/aluminum hydroxide (alum) was injected intraperitoneally to sensitize BALB/c mice over a period of 0 to 7 days, followed by challenge with 1% OVA. The treatment group received somatic antigens of protoscoleces emulsified with PBS on these days in each sensitization before being challenged with 1% OVA on days 14, 15, and 16. The effects of somatic antigens of protoscoleces on allergic airway inflammation were evaluated by examining histopathological changes, the recruitment of inflammatory cells in the bronchoalveolar lavage, cytokine production in the homogenized lung tissue (IL-4, IL-5, IL-10, IL-17, and IFN-γ), and total antioxidant capacity in serum.ResultsOverall, administration of somatic antigens of protoscoleces exacerbated allergic airway inflammation via increased Th2 cytokine levels in the lung homogenate, recruitment of eosinophils into bronchoalveolar lavage fluid, and pathological changes. In addition, total antioxidant capacity and IFN-γ levels declined following the administration of somatic antigens.ConclusionsThe results revealed that the co-administration of somatic products of protoscoleces with OVA/alum contributed to the exacerbation of allergic airway inflammation in BALB/c mice. Currently, the main cause of allergic-type inflammation exacerbation is unknown, and further research is needed to understand the mechanism of these interactions.Graphical