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JHEP Reports : Innovation in Hepatology Feb 2023Schistosomiasis is a parasitic infection which affects more than 200 million people globally. eggs, but not the adult worms, are mainly responsible for...
BACKGROUND & AIMS
Schistosomiasis is a parasitic infection which affects more than 200 million people globally. eggs, but not the adult worms, are mainly responsible for schistosomiasis-specific morbidity in the liver. It is unclear if eggs consume host metabolites, and how this compromises the host parenchyma.
METHODS
Metabolic reprogramming was analyzed by matrix-assisted laser desorption/ionization mass spectrometry imaging, liquid chromatography with high-resolution mass spectrometry, metabolite quantification, confocal laser scanning microscopy, live cell imaging, quantitative real-time PCR, western blotting, assessment of DNA damage, and immunohistology in hamster models and functional experiments in human cell lines. Major results were validated in human biopsies.
RESULTS
The infection with provokes hepatic exhaustion of neutral lipids and glycogen. Furthermore, the distribution of distinct lipid species and the regulation of rate-limiting metabolic enzymes is disrupted in the liver of infected animals. Notably, eggs mobilize, incorporate, and store host lipids, while the associated metabolic reprogramming causes oxidative stress-induced DNA damage in hepatocytes. Administration of reactive oxygen species scavengers ameliorates these deleterious effects.
CONCLUSIONS
Our findings indicate that eggs completely reprogram lipid and carbohydrate metabolism via soluble factors, which results in oxidative stress-induced cell damage in the host parenchyma.
IMPACT AND IMPLICATIONS
The authors demonstrate that soluble egg products of the parasite induce hepatocellular reprogramming, causing metabolic exhaustion and a strong redox imbalance. Notably, eggs mobilize, incorporate, and store host lipids, while the metabolic reprogramming causes oxidative stress-induced DNA damage in hepatocytes, independent of the host's immune response. eggs take advantage of the host environment through metabolic reprogramming of hepatocytes and enterocytes. By inducing DNA damage, this neglected tropical disease might promote hepatocellular damage and thus influence international health efforts.
PubMed: 36590323
DOI: 10.1016/j.jhepr.2022.100625 -
Parasitology Apr 2023Human schistosomiasis is caused by helminths of the genus . Macrophages play a crucial role in the immune regulation of this disease. These cells acquire different... (Review)
Review
Human schistosomiasis is caused by helminths of the genus . Macrophages play a crucial role in the immune regulation of this disease. These cells acquire different phenotypes depending on the type of stimulus they receive. M1 macrophages can be ‘classically activated’ and can display a proinflammatory phenotype. M2 or ‘alternatively activated’ macrophages are considered anti-inflammatory cells. Despite the relevance of macrophages in controlling infections, the role of the functional types of these cells in schistosomiasis is unclear. This review highlights different molecules and/or macrophage activation and polarization pathways during and infection. This review is based on original and review articles obtained through searches in major databases, including Scopus, Google Scholar, ACS, PubMed, Wiley, Scielo, Web of Science, LILACS and ScienceDirect. Our findings emphasize the importance of and antigens in macrophage polarization, as they exert immunomodulatory effects in different stages of the disease and are therefore important as therapeutic targets for schistosomiasis and in vaccine development. A combination of different antigens can provide greater protection, as it possibly stimulates an adequate immune response for an M1 or M2 profile and leads to host resistance; however, this warrants and studies.
Topics: Animals; Humans; Macrophage Activation; Schistosomiasis; Schistosomiasis japonica; Macrophages; Schistosoma mansoni
PubMed: 36601859
DOI: 10.1017/S0031182023000021 -
International Journal of Molecular... Jun 2020We characterized HSP40 (Sjp40) and HSP90α (Sjp90α) in this study. Western blot analysis revealed both are present in soluble egg antigens and egg secretory proteins,...
We characterized HSP40 (Sjp40) and HSP90α (Sjp90α) in this study. Western blot analysis revealed both are present in soluble egg antigens and egg secretory proteins, implicating them in triggering the host immune response after secretion from eggs into host tissues. These observations were confirmed by immunolocalization showing both HSPs are located in the Reynolds' layer within mature eggs, suggesting they are secreted by miracidia and accumulate between the envelope and the eggshell. Both HSPs are present in the musculature and parenchyma of adult males and in the vitelline cells of females; only Sjp90α is present on the tegument of adults. Sjp40 was able to enhance the expression of macrophages, dendritic cells, and eosinophilic cells in mouse liver non-parenchymal cells, whereas rSjp90α only stimulated the expression of dendritic cells. T helper 1 (Th1), Th2, and Th17 responses were increased upon rSjp40 stimulation in vitro, but rSjp90 only stimulated an increased Th17 response. Sjp40 has an important role in reducing the expression of fibrogenic gene markers in hepatic stellate cells in vitro. Overall, these findings provide new information on HSPs in improving our understanding of the pathological roles they play in their interaction with host immune cells.
Topics: Amino Acid Sequence; Animals; Antigens, Helminth; Disease Models, Animal; HSP40 Heat-Shock Proteins; HSP90 Heat-Shock Proteins; Helminth Proteins; Hepatic Stellate Cells; Immunohistochemistry; Liver; Mice; Models, Molecular; Protein Conformation; Schistosoma japonicum; Structure-Activity Relationship
PubMed: 32512920
DOI: 10.3390/ijms21114034 -
ACG Case Reports Journal May 2021Colorectal cancer (CRC) is one of the most common cancers worldwide, with increasing prevalence in Asian countries with a crude incidence of 21.1 per 100,000. is a...
Colorectal cancer (CRC) is one of the most common cancers worldwide, with increasing prevalence in Asian countries with a crude incidence of 21.1 per 100,000. is a genus of trematodes that infect millions of humans, affecting multiple organs, notably the intestines, liver, and bladder. Those trematodes may cause chronic inflammation in the affected organ leading to long-term complications such as fibrosis and neoplasia. There is rising evidence that infection with is correlated with the liver and CRC in endemic Asian countries. It is reported that chronic infection with Schistosomiasis raises the risk of CRC by 3 times. Less commonly seen outside of endemic areas, we present a case of -associated CRC in the United States in a woman with sigmoid adenocarcinoma and infection.
PubMed: 33997087
DOI: 10.14309/crj.0000000000000572 -
Frontiers in Immunology 2022The gut microbiota has been identified as a predictive biomarker for various diseases. However, few studies focused on the diagnostic accuracy of gut microbiota...
The gut microbiota has been identified as a predictive biomarker for various diseases. However, few studies focused on the diagnostic accuracy of gut microbiota derived-signature for predicting hepatic injuries in schistosomiasis. Here, we characterized the gut microbiomes from 94 human and mouse stool samples using 16S rRNA gene sequencing. The diversity and composition of gut microbiomes in infection-induced disease changed significantly. Gut microbes, such as , , , and , showed a significant correlation with the level of hepatic granuloma, fibrosis, hydroxyproline, ALT or AST in infection-induced disease. We identified a range of gut bacterial features to distinguish schistosomiasis from hepatic injuries using the random forest classifier model, LEfSe and STAMP analysis. Significant features , , and and their combinations have a robust predictive accuracy (AUC: from 0.8182 to 0.9639) for detecting liver injuries induced by infection in humans and mice. Our study revealed associations between gut microbiota features and physiopathology and serological shifts of schistosomiasis and provided preliminary evidence for novel gut microbiota-derived features for the non-invasive detection of schistosomiasis.
Topics: Animals; Bacteria; Bacteroides; Bacteroidetes; Gastrointestinal Microbiome; Humans; Liver Cirrhosis; Mice; RNA, Ribosomal, 16S; Schistosoma japonicum; Schistosomiasis
PubMed: 35911697
DOI: 10.3389/fimmu.2022.941530 -
Journal of Invertebrate Pathology May 2021Oncomelania hupensis is the only obligatory intermediate host of Schistosoma japonicum, the pathogen of zoonosis schistosomiasis. Haemocytes play a critical role in the...
Oncomelania hupensis is the only obligatory intermediate host of Schistosoma japonicum, the pathogen of zoonosis schistosomiasis. Haemocytes play a critical role in the cellular immune defence of O. hupensis against S. japonicum challenge. Here, the morphology and classification of haemocytes of O. hupensis were investigated by Giemsa staining and light microscopy, combining with the scanning and transmission electron microscopy and flow cytometry. Granulocytes and hyalinocytes were confirmed as two main types of haemocytes, account for ~ 10% and ~ 90% of all haemocytes, with size varying in 4.3-10.9 μm and 0.4-30.8 μm, respectively. Subpopulations can be identified further by granule feature, shape, size, and surface and inner structure of cells. The heterogeneity in morphology implied varied developmental process and function of haemocyte subpopulations. After the S. japonicum challenge, haemocytes of O. hupensis respond to S. japonicum invasion immediately. The dynamic change of haemocyte subpopulations indicates that the small hyalinocyte could differentiate into a larger one or granulocyte after S. japonicum challenge, and the granulocytes and larger hyalinocytes play leading roles in early defence reaction, but in different ways. Phagocytosis and apoptosis of haemocytes in O. hupensis were proved to be related to immune defence against S. japonicum, with the combined effect of granulocytes and larger hyalinocytes. However, the main pathway of each subpopulation to take effect in different periods need further investigation.
Topics: Animals; Hemocytes; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission; Schistosoma japonicum; Snails
PubMed: 33872572
DOI: 10.1016/j.jip.2021.107590 -
The Journal of Veterinary Medical... Oct 2019Humans and dogs live very close together and share various pathogens causing zoonotic parasitoses like schistosomiasis. A previous population genetics study done for...
Humans and dogs live very close together and share various pathogens causing zoonotic parasitoses like schistosomiasis. A previous population genetics study done for schistosomes in the Philippines suggested that there is a high transmission level of Schistosoma japonicum among humans and dogs proving that the latter are important reservoirs for this zoonotic parasite. A more sensitive and specific test detecting schistosome infection in dogs will therefore strengthen the zoonotic surveillance, which might help in the possible elimination of this ancient disease. In this study, recombinant thioredoxin peroxidase-1 (SjTPx-1) and tandem repeat proteins (Sj1TR, Sj2TR, Sj4TR, Sj7TR) previously tested on human and water buffalo samples were used to assess its diagnostic applicability to dogs. Fifty-nine dog serum and stool samples were collected in the schistosomiasis-endemic municipalities of Calatrava, Negros Occidental and Catarman, Northern Samar in the Philippines and examined using the ELISA as compared to microscopy and fecal sample-based PCR. Samples positive for Babesia gibsoni and Dirofilaria immitis were also used to check for cross-reaction. Results showed that SjTPx-1 (80% sensitivity, 92.3% specificity) and Sj7TR (73.3% sensitivity, 92.3% specificity) have good potentials for diagnosing S. japonicum infection in dogs. These diagnostic antigens will therefore improve the surveillance in the transmission of the parasites from dogs to humans.
Topics: Animals; Antigens, Helminth; Dogs; Enzyme-Linked Immunosorbent Assay; Peroxiredoxins; Philippines; Recombinant Proteins; Schistosoma japonicum; Schistosomiasis japonica
PubMed: 31391359
DOI: 10.1292/jvms.19-0126 -
Frontiers in Immunology 2020Schistosomiasis is a severe public health problem, which can cause tissue fibrosis and can even be fatal. Previous studies have proven that galectins and different kinds...
Schistosomiasis is a severe public health problem, which can cause tissue fibrosis and can even be fatal. Previous studies have proven that galectins and different kinds of cells involve in the regulation of tissue fibrosis process. In this study, outbred Kunming mice were infected with (). Our results showed that compared with uninfected mice, there were severe egg granulomatous inflammation and tissue fibrosis in the livers, spleens, and large intestines of -infected mice at 8 weeks post-infection (p.i.), and the number of eosinophils by hematoxylin and eosin staining and CD68 macrophage-positive area by immunohistochemical staining were significantly increased. Detected by using quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR), at 8 weeks after infection, the mRNA expression levels of galectin (Gal)-1, Gal-3, CD69, eosinophil protein X (EPX), and chitinase 3-like protein 3 (Ym1) were significantly increased in liver, spleen, and large intestine; eotaxin-1 (CCL11) and eosinophil cationic protein were significantly increased in both liver and spleen; eotaxin-2 (CCL24) and Arginase1 (Arg1) were significantly increased in both spleen and large intestine; and CD200R was significantly increased in both liver and large intestine. However, interleukin (IL)-1ß and inducible nitric oxide synthase (iNOS) were only significantly increased in liver. The M2/M1 ratio of CD200R/CD86 genes was significantly increased in liver, and ratios of Ym1/IL-1β and Ym1/iNOS were significantly increased in liver, spleen, and large intestine of -infected mice. study further confirmed that the levels of Gal-1, Gal-3, CD200R, Arg1, and Ym1 were significantly increased, and the ratios of CD200R/CD86 and Ym1/IL-1β were significantly increased in peritoneal macrophages isolated from -infected mice at 8 weeks p.i. In addition, correlation analysis showed that significant positive correlations existed between mRNA levels of Gal-1/Gal-3 and EPX in liver, between Gal-3 and Ym1 in both liver and large intestine, and between Gal-3 and CD200R in peritoneal macrophages of -infected mice. Our data suggested that Gal-1, Gal-3, eosinophils, and macrophages are likely involved in the development of egg granulomatous response and fibrosis induced by infection.
Topics: Animals; Disease Models, Animal; Eosinophil-Derived Neurotoxin; Eosinophils; Female; Fibrosis; Galectin 1; Galectin 3; Intestine, Large; Lectins; Liver; Macrophages, Peritoneal; Membrane Glycoproteins; Mice; RNA, Messenger; Schistosoma japonicum; Schistosomiasis japonica; Spleen; beta-N-Acetylhexosaminidases
PubMed: 32231658
DOI: 10.3389/fimmu.2020.00146 -
Experimental Parasitology May 2021Molecular diagnostics are powerful tools for disease detection but are typically confined to the laboratory environment due to the cumbersome methods required to extract...
Molecular diagnostics are powerful tools for disease detection but are typically confined to the laboratory environment due to the cumbersome methods required to extract nucleic acids from biological samples. Accurate diagnosis is essential for early detection of parasitic worm infections and for monitoring control programs, particularly during new transmission outbreaks to limit infection spread. We optimized the recently developed DNA dipstick technology to purify Schistosoma japonicum DNA from different life stages in <60 s. We successfully detected DNA from adult worms, eggs and infected snails. The speed and simplicity of this method enables the point-of-care detection of S. japonicum.
Topics: Animals; DNA, Helminth; Liver; Mice; Molecular Diagnostic Techniques; Nucleic Acid Amplification Techniques; Point-of-Care Testing; Real-Time Polymerase Chain Reaction; Schistosoma japonicum; Schistosomiasis japonica; Snails
PubMed: 33713659
DOI: 10.1016/j.exppara.2021.108098 -
PLoS Pathogens Jul 2023Schistosomiasis, a severe parasitic disease, is primarily caused by Schistosoma mansoni, Schistosoma japonicum, or Schistosoma haematobium. Currently, praziquantel is... (Review)
Review
Schistosomiasis, a severe parasitic disease, is primarily caused by Schistosoma mansoni, Schistosoma japonicum, or Schistosoma haematobium. Currently, praziquantel is the only recommended drug for human schistosome infection. However, the lack of efficacy of praziquantel against juvenile worms and concerns about the emergence of drug resistance are driving forces behind the research for an alternative medication. Schistosomes are obligatory parasites that survive on nutrients obtained from their host. The ability of nutrient uptake depends on their physiological structure. In short, the formation and maintenance of the structure and nutrient supply are mutually reinforcing and interdependent. In this review, we focus on the structural features of the tegument, esophagus, and intestine of schistosomes and their roles in nutrient acquisition. Moreover, we introduce the significance and modes of glucose, lipids, proteins, and amino acids intake in schistosomes. We linked the schistosome structure and nutrient supply, introduced the currently emerging targets, and analyzed the current bottlenecks in the research and development of drugs and vaccines, in the hope of providing new strategies for the prevention and control of schistosomiasis.
Topics: Animals; Humans; Praziquantel; Schistosomiasis; Schistosoma japonicum; Schistosoma haematobium; Schistosoma mansoni; Eating
PubMed: 37498810
DOI: 10.1371/journal.ppat.1011498