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Frontiers in Immunology 2020The parasitic worms, and , reside in the mesenteric veins, where they release eggs that induce a dramatic granulomatous response in the liver and intestines.... (Review)
Review
The parasitic worms, and , reside in the mesenteric veins, where they release eggs that induce a dramatic granulomatous response in the liver and intestines. Subsequently, infection may further develop into significant fibrosis and portal hypertension. Over the past several years, uncovering the mechanism of immunopathology in schistosomiasis has become a major research objective. It is known that T lymphocytes, especially CD4 T cells, are essential for immune responses against species. However, obtaining a clear understanding of how T lymphocytes regulate the pathological process is proving to be a daunting challenge. To date, CD4 T cell subsets have been classified into several distinct T helper (Th) phenotypes including Th1, Th2, Th17, T follicular helper cells (Tfh), Th9, and regulatory T cells (Tregs). In the case of schistosomiasis, the granulomatous inflammation and the chronic liver pathology are critically regulated by the Th1/Th2 responses. Animal studies suggest that there is a moderate Th1 response to parasite antigens during the acute stage, but then, egg-derived antigens induce a sustained and dominant Th2 response that mediates granuloma formation and liver fibrosis. In addition, the newly discovered Th17 cells also play a critical role in the hepatic immunopathology of schistosomiasis. Within the liver, Tregs are recruited to hepatic granulomas and exert an immunosuppressive role to limit the granulomatous inflammation and fibrosis. Moreover, recent studies have shown that Tfh and Th9 cells might also promote liver granulomas and fibrogenesis in the murine schistosomiasis. Thus, during infection, T-cell subsets undergo complicated cross-talk with antigen presenting cells that then defines their various roles in the local microenvironment for regulating the pathological progression of schistosomiasis. This current review summarizes a vast body of literature to elucidate the contribution of T lymphocytes and their associated cytokines in the immunopathology of schistosomiasis.
Topics: Animals; CD4-Positive T-Lymphocytes; Cytokines; Granuloma; Humans; Liver; Liver Cirrhosis; Mice; Schistosoma japonicum; Schistosoma mansoni; Schistosomiasis; T Follicular Helper Cells; T-Lymphocyte Subsets; Th1 Cells; Th17 Cells; Th2 Cells
PubMed: 32132991
DOI: 10.3389/fimmu.2020.00061 -
International Journal of Molecular... Jan 2024Control of schistosomiasis japonica, endemic in Asia, including the Philippines, China, and Indonesia, is extremely challenging. is a highly pathogenic helminth... (Review)
Review
Control of schistosomiasis japonica, endemic in Asia, including the Philippines, China, and Indonesia, is extremely challenging. is a highly pathogenic helminth parasite, with disease arising predominantly from an immune reaction to entrapped parasite eggs in tissues. Females of this species can generate 1000-2200 eggs per day, which is about 3- to 15-fold greater than the egg output of other schistosome species. Bovines (water buffalo and cattle) are the predominant definitive hosts and are estimated to generate up to 90% of parasite eggs released into the environment in rural endemic areas where these hosts and humans are present. Here, we highlight the necessity of developing veterinary transmission-blocking vaccines for bovines to better control the disease and review potential vaccine candidates. We also point out that the approach to producing efficacious transmission-blocking animal-based vaccines before moving on to human vaccines is crucial. This will result in effective and feasible public health outcomes in agreement with the One Health concept to achieve optimum health for people, animals, and the environment. Indeed, incorporating a veterinary-based transmission vaccine, coupled with interventions such as human mass drug administration, improved sanitation and hygiene, health education, and snail control, would be invaluable to eliminating zoonotic schistosomiasis.
Topics: Animals; Female; Cattle; Humans; Schistosomiasis japonica; Schistosoma japonicum; Vaccines; Schistosomiasis; Vaccination; China; Buffaloes
PubMed: 38338980
DOI: 10.3390/ijms25031707 -
Parasites & Vectors Oct 2023Schistosoma infection is a significant public health issue, affecting over 200 million individuals and threatening 700 million people worldwide. The species prevalent in...
BACKGROUND
Schistosoma infection is a significant public health issue, affecting over 200 million individuals and threatening 700 million people worldwide. The species prevalent in China is Schistosoma japonicum. Recent studies showed that both gut microbiota and metabolome are closely related to schistosomiasis caused by S. japonicum, but clinical study is limited and the underlying mechanism is largely unclear. This study aimed to explore alterations as well as function of gut microbiota and metabolite profile in the patients with S. japonicum infection.
METHODS
This study included 20 patients diagnosed with chronic schistosomiasis caused by S. japonicum, eight patients with advanced schistosomiasis caused by S. japonicum and 13 healthy volunteers. The fresh feces of these participators, clinical examination results and basic information were collected. 16S ribosomal RNA gene sequencing was used to investigate gut microbiota, while ultraperformance liquid chromatography-mass spectrometry (UHPLC-MS) was applied to explore the metabolome of patients in different stages of schistosomiasis.
RESULTS
The study found that gut microbiota and metabolites were altered in patients with different stages of S. japonicum infection. Compared with healthy control group, the gut microbial diversity in patients with chronic S. japonicum infection was decreased significantly. However, the diversity of gut microbiota in patients with chronic schistosomiasis was similar to that in patients with advanced schistosomiasis. Compared with uninfected people, patients with schistosomiasis showed decreased Firmicutes and increased Proteobacteria. As disease progressed, Firmicutes was further reduced in patients with advanced S. japonicum infection, while Proteobacteria was further increased. In addition, the most altered metabolites in patients with S. japonicum infection were lipids and lipid-like molecules as well as organo-heterocyclic compounds, correlated with the clinical manifestations and disease progress of schistosomiasis caused by S. japonicum.
CONCLUSIONS
This study suggested that the gut microbiota and metabolome altered in patients in different stages of schistosomiasis, which was correlated with progression of schistosomiasis caused by S. japonicum. This inter-omics analysis may shed light on a better understanding of the mechanisms of the progression of S. japonicum infection and contribute to identifying new potential targets for the diagnosis and prognosis of S. japonicum infection. However, a large sample size of validation in clinic is needed, and further study is required to investigate the underlying mechanism.
Topics: Animals; Humans; Schistosomiasis japonica; Gastrointestinal Microbiome; Schistosoma japonicum; Schistosomiasis; China
PubMed: 37798771
DOI: 10.1186/s13071-023-05970-3 -
Visceral Medicine Aug 2023Despite long-term preventative efforts by local public health authorities, the prevalence of fluke infection remains high in specific areas in eastern and southeastern... (Review)
Review
BACKGROUND
Despite long-term preventative efforts by local public health authorities, the prevalence of fluke infection remains high in specific areas in eastern and southeastern Asia. Recently increasing travel or migration activities have led to the transfer and spread of such infections from endemic areas to other regions.
SUMMARY
The epidemiology, clinical signs, and symptoms for three common blood and liver flukes, namely , , and , are described in this review, and their current diagnosis and management strategy are reviewed. These flukes are considered clinically important because of the increased risk of liver or biliary cancer.
KEY MESSAGES
Early treatment and prevention of disease spread can reduce the incidence of related hepatobiliary cancer. Recognition of these fluke infection is essential for a correct diagnosis and early treatment to prevent the development of deadly cancers.
PubMed: 37901386
DOI: 10.1159/000531599 -
Parasite Immunology Feb 2021Schistosomiasis is the most important helminth disease in the world from a public health perspective. S mansoni and S japonicum account for the majority of global... (Review)
Review
Schistosomiasis is the most important helminth disease in the world from a public health perspective. S mansoni and S japonicum account for the majority of global intestinal schistosomiasis cases, and the pathogenesis is widely assumed to be fundamentally similar. However, the majority of research on schistosomiasis has been carried out on S mansoni and comparisons between the two species are rarely made. Here, we will discuss aspects of both older and recent literature where such comparisons have been made, with a particular focus on the pathological agent, the host granulomatous response to the egg. Major differences between the two species are apparent in features such as egg production patterns and cellular infiltration; however, it is also clear that even subtle differences in the cascade of various cytokines and chemokines contribute to the different levels of pathology observed between these two main species of intestinal schistosomiasis. A better understanding of such differences at species level will be vital when it comes to the development of new treatment strategies and vaccines.
Topics: Animals; Chemokines; Cytokines; Granuloma; Humans; Schistosoma japonicum; Schistosoma mansoni; Schistosomiasis japonica; Schistosomiasis mansoni; Vaccines
PubMed: 32692855
DOI: 10.1111/pim.12778 -
EBioMedicine Aug 2023Schistosomiasis is a disease that significantly impacts human health in the developing world. Effective diagnostics are urgently needed for improved control of this...
BACKGROUND
Schistosomiasis is a disease that significantly impacts human health in the developing world. Effective diagnostics are urgently needed for improved control of this disease. CRISPR-based technology has rapidly accelerated the development of a revolutionary and powerful diagnostics platform, resulting in the advancement of a class of ultrasensitive, specific, cost-effective and portable diagnostics, typified by applications in COVID-19/cancer diagnosis.
METHODS
We developed CRISPR-based diagnostic platform SHERLOCK (Specific High-sensitivity Enzymatic Reporter unLOCKing) for the detection of Schistosoma japonicum and S. mansoni by combining recombinase polymerase amplification (RPA) with CRISPR-Cas13a detection, measured via fluorescent or colorimetric readouts. We evaluated SHERLOCK assays by using 150 faecal/serum samples collected from Schistosoma-infected ARC Swiss mice (female), and 189 human faecal/serum samples obtained from a S. japonicum-endemic area in the Philippines and a S. mansoni-endemic area in Uganda.
FINDINGS
The S. japonicum SHERLOCK assay achieved 93-100% concordance with gold-standard qPCR detection across all the samples. The S. mansoni SHERLOCK assay demonstrated higher sensitivity than qPCR and was able to detect infection in mouse serum as early as 3 weeks post-infection. In human samples, S. mansoni SHERLOCK had 100% sensitivity when compared to qPCR of faecal and serum samples.
INTERPRETATION
These schistosomiasis diagnostic assays demonstrate the potential of SHERLOCK/CRISPR-based diagnostics to provide highly accurate and field-friendly point-of-care tests that could provide the next generation of diagnostic and surveillance tools for parasitic neglected tropical diseases.
FUNDING
Australian Infectious Diseases Research Centre seed grant (2022) and National Health and Medical Research Council (NHMRC) of Australia (APP1194462, APP2008433).
Topics: Humans; Female; Animals; Mice; Sensitivity and Specificity; Australia; COVID-19; Schistosomiasis; Schistosoma japonicum; COVID-19 Testing
PubMed: 37487416
DOI: 10.1016/j.ebiom.2023.104730 -
Parasite Immunology Jun 2022Schistosomiasis is a chronic human parasitic disease that causes serious health problems worldwide. The disease-associated liver pathology is one of the hallmarks of... (Review)
Review
Schistosomiasis is a chronic human parasitic disease that causes serious health problems worldwide. The disease-associated liver pathology is one of the hallmarks of infections by Schistosoma mansoni and Schistosoma japonicum, and is accountable for the debilitating condition found in infected patients. In the past few years, investigative studies have highlighted the key role played by neutrophils and the influence of inflammasome signalling pathway in different pathological conditions. However, it is noteworthy that the study of inflammasome activation in neutrophils has been overlooked by reports concerning macrophages and monocytes. This interplay between neutrophils and inflammasomes is much more poorly investigated during schistosomiasis. Herein, we reviewed the role of neutrophils during schistosomiasis and addressed the potential connection between these cells and inflammasome activation in this context.
Topics: Animals; Humans; Inflammasomes; Liver Diseases; Neutrophils; Schistosoma japonicum; Schistosoma mansoni; Schistosomiasis
PubMed: 35332932
DOI: 10.1111/pim.12916 -
Parasitology Research May 2020Schistosomiasis is still prevalent and seriously endangering the health of people and livestock in many countries. There have been great efforts to develop vaccines...
Schistosomiasis is still prevalent and seriously endangering the health of people and livestock in many countries. There have been great efforts to develop vaccines against schistosomiasis for prolonged protection in epidemic areas. Molecules from lung-stage schistosomula have been regarded as potential vaccine candidates against schistosomiasis. Our previous work has shown that cathepsin L3 from Schistosoma japonicum (SjCL3) is expressed in lung-stage schistosomula, but its role is not well known. In the present study, we characterized SjCL3 and detected its effect as a possible vaccine in vivo and in vitro. From the results of quantitative PCR (qPCR) and western blot, SjCL3 was present throughout the lifecycle of the worm, and its relative expressed level was higher in the liver eggs and adult worms than other stages. Additionally, immunofluorescence assay showed that SjCL3 was mainly concentrated in the eggshell, alimentary canal, and musculature of worms. Compared with the adjuvant group, the immunization of SjCL3 in mice resulted in a 28.9% decrease in worm burden and a 29.2% reduction in egg number in the host liver. In antibody-dependent cell-mediated cytotoxicity (ADCC) insecticidal experiments in vitro, the existence of SjCL3 could in part suppress adherence between macrophages and worm. The above results indicated that the immunization of SjCL3 could induce limited immune protection against S. japonicum infection in mice, and this protease played a role in breaking the process of ADCC, which was beneficial to the survival of worms.
Topics: Adjuvants, Immunologic; Animals; Antibody-Dependent Cell Cytotoxicity; Blotting, Western; Cathepsins; Cloning, Molecular; Female; Macrophages; Mice; Mice, Inbred BALB C; Protozoan Vaccines; Schistosoma japonicum; Schistosomiasis japonica; Vaccination
PubMed: 32185481
DOI: 10.1007/s00436-020-06647-x -
Parasitology Apr 2020Only with the completion of the life cycles of Fasciola hepatica in 1883 and 30 years later those of Schistosoma japonicum (1913), Schistosoma haematobium and... (Review)
Review
Only with the completion of the life cycles of Fasciola hepatica in 1883 and 30 years later those of Schistosoma japonicum (1913), Schistosoma haematobium and Schistosoma mansoni (1915) did research on schistosomiasis really get underway. One of the first papers by Cawston in 1918, describing attempts to establish the means of transmission of S. haematobium in Natal, South Africa, forms the historical perspective against which to judge where we are now. Molecular biology techniques have produced a much better definition of the complexity of the schistosome species and their snail hosts, but also revealed the extent of hybridization between human and animal schistosomes that may impact on parasite adaptability. While diagnostics have greatly improved, the ability to detect single worm pair infections routinely, still falls short of its goal. The introduction of praziquantel ~1982 has revolutionized the treatment of infected individuals and led directly to the mass drug administration programmes. In turn, the severe pathological consequences of high worm burdens have been minimized, and for S. haematobium infections the incidence of associated squamous cell carcinoma has been reduced. In comparison, the development of effective vaccines has yet to come to fruition. The elimination of schistosomiasis japonica from Japan shows what is possible, using multiple lines of approach, but the clear and present danger is that the whole edifice of schistosome control is balanced on the monotherapy of praziquantel, and the development of drug resistance could topple that.
Topics: Animals; Carcinoma, Squamous Cell; Drug Resistance; History, 20th Century; History, 21st Century; Humans; Life Cycle Stages; Praziquantel; Schistosoma haematobium; Schistosoma japonicum; Schistosoma mansoni; Schistosomiasis; Snails; Vaccines
PubMed: 31965953
DOI: 10.1017/S0031182020000049 -
PLoS Neglected Tropical Diseases Jun 2023Identification of promising schistosome antigen targets is crucial for the development of anti-schistosomal strategies. Schistosomes rely on their neuromuscular systems...
Identification of promising schistosome antigen targets is crucial for the development of anti-schistosomal strategies. Schistosomes rely on their neuromuscular systems to coordinate important locomotory behaviors. Tyrosine hydroxylase (TH) is critical in the initial rate-limiting step in biosynthesis of catecholamine, the important neuroactive agents, which promote the lengthening of the worm through muscular relaxation and are therefore of great importance to the movement of the organism both within and between its hosts. THs from both Schistosoma mansoni and Schistosoma japonicum and their enzyme activities have been discovered; however, the role of these proteins during infection have not been explored. Herein, a recombinant protein of the nonconserved fragment of S. japonicum TH (SjTH) was produced and the corresponding polyclonal antibody was generated. The expression and antigenicity of SjTH were detected by qRT-PCR, western blotting, immunofluorescence assays, and ELISA. Mice immunized with the recombinant SjTH were challenged with cercariae to evaluate the immunoprotective value of this protein. Our results showed SjTH not only distributed in the head associated with the central nervous system, but also expressed along the tegument and the intestinal intima, which are involved in the movement, coupling and digestion of the parasites and associated with the peripheral nervous system. This protein can effectively stimulate humoral immune responses in mammalian hosts and has high potential as a biomarker for schistosomiasis immunodiagnosis. Furthermore, immunization with recombinant SjTH showed to reduce the worm and egg burden of challenged mice, and to contribute to the systemic balance of the Th1/Th2 responses. Taken together, these results suggest that SjTH is an important pathogenic molecule in S. japonicum and may be a possible target for anti-schistosomal approaches.
Topics: Animals; Mice; Schistosoma japonicum; Schistosomiasis japonica; Tyrosine 3-Monooxygenase; Schistosomiasis; Immunologic Tests; Mammals
PubMed: 37276235
DOI: 10.1371/journal.pntd.0011389