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Parasite Immunology Mar 2024Long-term infection of schistosomiasis will seriously affect the liver health of patients. The serum of 334 chronic Schistosoma japonicum patients and 149 healthy...
Long-term infection of schistosomiasis will seriously affect the liver health of patients. The serum of 334 chronic Schistosoma japonicum patients and 149 healthy volunteers was collected. Compared with heathy people, the level of C4 (complement 4) was increased, and the level of C3 (complement 3) was in an obvious skewed distribution. ELISA was performed to detect the serum cytokines, the results showed that the levels of IFN-γ (interferon-γ), IL (interleukin)-2 and TNF-α (tumour necrosis factor-α) were reduced, while the levels of Th2 cytokines (IL-4, IL-6 and IL-10) were increased. In the serum of patients with high C3, the secretion of HA (hyaluronic acid), LN (laminin), IV-C (type IV collagen) and PCIII (type III procollagen) were increased, the activation of hepatic stellate cells was promoted. Exogenous human recombinant C3 made mice liver structure of the mice damaged and collagen deposition. IFN-γ and IFN-γ/IL-4 were decreased, while HA, LN, PCIII and IV-C were increased, and the expressions of α-SMA and TGF-β1 in liver tissues were up-regulated. However, the addition of IFN-γ partially reversed the effect of C3 on promoting fibrosis. High level of C3 is associated with Th2 immune response and liver fibrosis in patients with schistosomiasis.
Topics: Humans; Mice; Animals; Interleukin-4; Liver Cirrhosis; Schistosomiasis; Liver; Cytokines; Tumor Necrosis Factor-alpha; Immunity; Schistosomiasis japonica
PubMed: 38465509
DOI: 10.1111/pim.13029 -
Parasites & Vectors Mar 2024Schistosomiasis is a disease primarily caused by eggs laid by pathogens called schistosomes. Among the schistosome species infecting humans, Schistosoma japonicum...
BACKGROUND
Schistosomiasis is a disease primarily caused by eggs laid by pathogens called schistosomes. Among the schistosome species infecting humans, Schistosoma japonicum possesses the largest fecundity; each adult female produces an average of 3500 eggs per day. The lack of proper culture conditions supporting continuous oviposition in vitro has precluded detailed investigation of mechanisms regulating sexual maturation and egg production in Schistosoma japonicum.
METHODS
We optimized in vitro culture conditions by replacing reagents that are part of the classical ABC169 medium. Fast Blue BB staining and 4',6-diamidino-2-phenylindole (DAPI) labeling were applied to observe the sexual development status of the females. In vitro RNA interference (RNAi) technology was used to validate the capability of the modified medium. The detection of male β-alanyl-tryptamine (BATT) was conducted using liquid chromatography-mass spectrometry (LC-MS).
RESULTS
Both m-AB169 (1640) and AB169 (1640) media are capable of facilitating the sexual development of paired virgin female S. japonicum, as well as sustaining the mature reproductive organs and egg production of adult S. japonicum for at least 22 days in vitro. M-AB169 (1640) provided a more stable condition for supporting the sexual maturity of female S. japonicum, as evidenced by the consistent initiation of egg production compared with AB169 (1640). Through a comparative analysis of S. japonicum and S. mansoni in diverse media, we demonstrated that these closely related species display distinct demands for their sexual development and egg production, suggesting a potential influence of nutritional factors on the observed variations in host ranges among different schistosome species. Importantly, we successfully identified the presence of the pheromone β-alanyl-tryptamine (BATT) in S. japonicum, previously identified in S. mansoni, highlighting its conserved role in schistosome reproductive development. Through the employment of double-stranded RNA (dsRNA) treatment to silence two genes that are involved in either the male (gli1, glioma-associated oncogene homolog 1) or female (vf1, vitellogenic factor 1) side in male-induced female reproductive development of S. mansoni, we confirmed that the combination of m-AB169 (1640) and RNAi technology has the capacity to facilitate in vitro studies of S. japonicum's reproductive and oviposition processes.
CONCLUSIONS
We developed a novel medium, m-AB169 (1640), that not only maintains the mature reproductive organs and continuous oviposition of adult female Schistosoma japonicum for up to 22 days but also supports the reproductive development and subsequent egg-laying of virgin females after pairing with male worms. This study provides a valuable in vitro platform for functional studies of the mechanisms underlying the fascinating biology of the female sexual development and egg production of S. japonicum, which may accelerate the development of new strategies targeting schistosome egg production.
Topics: Humans; Animals; Male; Female; Schistosoma japonicum; Oviposition; Reproduction; Genitalia, Female; Schistosomatidae; Tryptamines
PubMed: 38454463
DOI: 10.1186/s13071-024-06191-y -
Parasites & Vectors Mar 2024Schistosomiasis, a neglected tropical disease, remains an important public health problem. Although there are various methods for diagnosing schistosomiasis, many...
BACKGROUND
Schistosomiasis, a neglected tropical disease, remains an important public health problem. Although there are various methods for diagnosing schistosomiasis, many limitations still exist. Early diagnosis and treatment of schistosomiasis can significantly improve survival and prognosis of patients.
METHODOLOGY
Circulating cell-free (cf)DNA has been widely used in the diagnosis of various diseases. In our study, we evaluated the diagnostic value of circulating cfDNA for schistosomiasis caused by Schistosoma japonicum. We focused on the tandem sequences and mitochondrial genes of S. japonicum to identify highly sensitive and specific targets for diagnosis of Schistosomiasis japonica.
RESULTS
Through data screening and analysis, we ultimately identified four specific tandem sequences (TD-1, TD-2, TD-3. and TD-4) and six mitochondrial genes (COX1(1), COX1(2), CYTB, ATP6, COX3, and ND5). We designed specific primers to detect the amount of circulating cfDNA in S. japonicum-infected mouse and chronic schistosomiasis patients. Our results showed that the number of tandem sequences was significantly higher than that of the mitochondrial genes. A S. japonicum infection model in mice suggested that infection of S. japonicum can be diagnosed by detecting circulating cfDNA as early as the first week. We measured the expression levels of circulating cfDNA (TD-1, TD-2, and TD-3) at different time points and found that TD-3 expression was significantly higher than that of TD-1 or TD-2. We also infected mice with different quantities of cercariae (20 s and 80 s). The level of cfDNA (TD-3) in the 80 s infection group was significantly higher than in the 20 s infection group. Additionally, cfDNA (TD-3) levels increased after egg deposition. Meanwhile, we tested 42 patients with chronic Schistosomiasis japonica and circulating cfDNA (TD-3) was detected in nine patients.
CONCLUSIONS
We have screened highly sensitive targets for the diagnosis of Schistosomiasis japonica, and the detection of circulating cfDNA is a rapid and effective method for the diagnosis of Schistosomiasis japonica. The levels of cfDNA is correlated with cercariae infection severity. Early detection and diagnosis of schistosomiasis is crucial for patient treatment and improving prognosis.
Topics: Humans; Animals; Mice; Schistosomiasis japonica; Biomarkers; Schistosoma japonicum; Cell-Free Nucleic Acids; Cercaria
PubMed: 38449022
DOI: 10.1186/s13071-024-06203-x -
Microbiology Spectrum Apr 2024Schistosomiasis japonica is one of the neglected tropical diseases characterized by chronic hepatic, intestinal granulomatous inflammation and fibrosis, as well as...
UNLABELLED
Schistosomiasis japonica is one of the neglected tropical diseases characterized by chronic hepatic, intestinal granulomatous inflammation and fibrosis, as well as dysbiosis of intestinal microbiome. Previously, the probiotic has been shown to alleviate the pathological injuries in mice infected with by improving the disturbance of the intestinal microbiota. However, the underlying mechanisms involved in this process remain unclear. In this study, metagenomics sequencing and functional analysis were employed to investigate the differential changes in taxonomic composition and functional genes of the intestinal microbiome in infected mice treated with . The results revealed that intervention with altered the taxonomic composition of the intestinal microbiota at the species level in infected mice and significantly increased the abundance of beneficial bacteria. Moreover, the abundance of predicted genes in the intestinal microbiome was also significantly changed, and the abundance of and genes translated to urease was significantly restored. Further analysis showed that was positively correlated with several KEGG Orthology (KO) genes and metabolic reactions, which might play important roles in alleviating the pathological symptoms caused by infection, indicating that it has the potential to function as another effective therapeutic agent for schistosomiasis. These data suggested that treatment of murine schistosomiasis japonica by might be induced by alterations in the taxonomic composition and functional gene of the intestinal microbiome in mice. We hope this study will provide adjuvant strategies and methods for the early prevention and treatment of schistosomiasis japonica.
IMPORTANCE
Targeted interventions of probiotics on gut microbiome were used to explore the mechanism of alleviating schistosomiasis japonica. Through metagenomic analysis, there were significant changes in the composition of gut microbiota in mice infected with and significant increase in the abundance of beneficial bacteria after the intervention of . At the same time, the abundance of functional genes was found to change significantly. The abundance of genes related to urease metabolism and related to D-erythrose 4-phosphate production was significantly restored, highlighting the importance of in the recovery and abundance of predicted genes of the gut microbiome. These results indicated potential regulatory mechanism between the gene function of gut microbiome and host immune response. Our research lays the foundation for elucidating the regulatory mechanism of probiotic intervention in alleviating schistosomiasis japonica, and provides potential adjuvant treatment strategies for early prevention and treatment of schistosomiasis japonica.
Topics: Animals; Mice; Schistosomiasis japonica; Gastrointestinal Microbiome; Bacillus amyloliquefaciens; Urease; Schistosoma japonicum; Bacteria
PubMed: 38441977
DOI: 10.1128/spectrum.03735-23 -
JCI Insight Mar 2024Programmed cell death protein 1 (PD-1), a coinhibitory T cell checkpoint, is also expressed on macrophages in pathogen- or tumor-driven chronic inflammation. Increasing...
Programmed cell death protein 1 (PD-1), a coinhibitory T cell checkpoint, is also expressed on macrophages in pathogen- or tumor-driven chronic inflammation. Increasing evidence underscores the importance of PD-1 on macrophages for dampening immune responses. However, the mechanism governing PD-1 expression in macrophages in chronic inflammation remains largely unknown. TGF-β1 is abundant within chronic inflammatory microenvironments. Here, based on public databases, significantly positive correlations between PDCD1 and TGFB1 gene expression were observed in most human tumors. Of note, among immune infiltrates, macrophages as the predominant infiltrate expressed higher PDCD1 and TGFBR1/TGFBR2 genes. MC38 colon cancer and Schistosoma japonicum infection were used as experimental models for chronic inflammation. PD-1hi macrophages from chronic inflammatory tissues displayed an immunoregulatory pattern and expressed a higher level of TGF-β receptors. Either TGF-β1-neutralizing antibody administration or macrophage-specific Tgfbr1 knockdown largely reduced PD-1 expression on macrophages in animal models. We further demonstrated that TGF-β1 directly induced PD-1 expression on macrophages. Mechanistically, TGF-β1-induced PD-1 expression on macrophages was dependent on SMAD3 and STAT3, which formed a complex at the Pdcd1 promoter. Collectively, our study shows that macrophages adapt to chronic inflammation through TGF-β1-triggered cooperative SMAD3/STAT3 signaling that induces PD-1 expression and modulates macrophage function.
Topics: Animals; Humans; Transforming Growth Factor beta1; Receptor, Transforming Growth Factor-beta Type I; Programmed Cell Death 1 Receptor; Macrophages; Inflammation; Smad3 Protein; STAT3 Transcription Factor
PubMed: 38441961
DOI: 10.1172/jci.insight.165544 -
Acta Parasitologica Mar 2024The Government of Indonesia committed to eliminating schistosomiasis by 2025. Collaboratively snail control became one of the crucial strategies to ensure that the...
PURPOSE
The Government of Indonesia committed to eliminating schistosomiasis by 2025. Collaboratively snail control became one of the crucial strategies to ensure that the prevalence of Schistosoma japonicum in Oncomelania hupensis lindoensis reaches zero by the end of the program. This research investigated the spatial cluster change of S. japonicum transmission foci in Indonesia between 2017 and 2021.
METHODS
We mapped the snail foci, collected the snails, and calculated the snail density. We also conducted laboratory tests to detect the existence of cercariae in the snails. Identified infected snails were used to calculate the infection rate (IR) or snails' prevalence of schistosome cercariae among freshwater snails. We then analysed the spatial cluster using the Getis-Ord Gi* statistic to identify the hot and cold spots.
RESULTS
The 5-year schistosomiasis elimination program successfully declined 18.84% of the snail foci and reduced 40.37% of the infected snail foci. Local spatial autocorrelation of snail density and infection rate identified that in 2017 and 2021, the number of cold spots decreased by 53.91% and 0%, while hot spots increased by 2.63% and 56.1%. The presence of more hot spots suggests a rise in the number of foci with high snail density and infection rates. The implementation of snail control was not optimal, and the parasite transmission through domestic animals still existed, causing the spatial cluster of hot spots to change during this period. Most hotspots have been observed near settlements, primarily in cocoa plantations, developed and deserted rice fields, grassland, and bush wetlands.
CONCLUSION
During the schistosomiasis elimination program, the number of hot spots increased while cold spots decreased, and there were notable changes in the geographical distribution of hot spots, indicating a shift in the clustering pattern of schistosomiasis cases. The findings become essential for policymakers, particularly in selecting priority areas for intervention. In the Discussion section, we demonstrated the selection process based on the existence of hot and cold spots. Furthermore, we proposed that enhancing cross-sector integration is crucial, particularly in connection with the management of S. japonicum transmission through domestic animals.
Topics: Animals; Indonesia; Snails; Schistosoma japonicum; Schistosomiasis japonica; Disease Eradication; Humans; Spatial Analysis
PubMed: 38416327
DOI: 10.1007/s11686-024-00802-5 -
Infectious Diseases of Poverty Feb 2024Schistosoma japonicum is a parasitic flatworm that causes human schistosomiasis, which is a significant cause of morbidity in China, the Philippines and Indonesia....
BACKGROUND
Schistosoma japonicum is a parasitic flatworm that causes human schistosomiasis, which is a significant cause of morbidity in China, the Philippines and Indonesia. Oncomelania hupensis (Gastropoda: Pomatiopsidae) is the unique intermediate host of S. japonicum. A complete genome sequence of O. hupensis will enable the fundamental understanding of snail biology as well as its co-evolution with the S. japonicum parasite. Assembling a high-quality reference genome of O. hupehensis will provide data for further research on the snail biology and controlling the spread of S. japonicum.
METHODS
The draft genome was de novo assembly using the long-read sequencing technology (PacBio Sequel II) and corrected with Illumina sequencing data. Then, using Hi-C sequencing data, the genome was assembled at the chromosomal level. CAFE was used to do analysis of contraction and expansion of the gene family and CodeML module in PAML was used for positive selection analysis in protein coding sequences.
RESULTS
A total length of 1.46 Gb high-quality O. hupensis genome with 17 unique full-length chromosomes (2n = 34) of the individual including a contig N50 of 1.35 Mb and a scaffold N50 of 75.08 Mb. Additionally, 95.03% of these contig sequences were anchored in 17 chromosomes. After scanning the assembled genome, a total of 30,604 protein-coding genes were predicted. Among them, 86.67% were functionally annotated. Further phylogenetic analysis revealed that O. hupensis was separated from a common ancestor of Pomacea canaliculata and Bellamya purificata approximately 170 million years ago. Comparing the genome of O. hupensis with its most recent common ancestor, it showed 266 significantly expanded and 58 significantly contracted gene families (P < 0.05). Functional enrichment of the expanded gene families indicated that they were mainly involved with intracellular, DNA-mediated transposition, DNA integration and transposase activity.
CONCLUSIONS
Integrated use of multiple sequencing technologies, we have successfully constructed the genome at the chromosomal-level of O. hupensis. These data will not only provide the compressive genomic information, but also benefit future work on population genetics of this snail as well as evolutional studies between S. japonicum and the snail host.
Topics: Animals; Humans; Schistosoma japonicum; Phylogeny; Gastropoda; Chromosomes; DNA; China
PubMed: 38414088
DOI: 10.1186/s40249-024-01187-3 -
Zhongguo Xue Xi Chong Bing Fang Zhi Za... Dec 2023To compare the efficiency of multiple etiological techniques for detection of infections in wild mice, so as to provide technical supports to assessment of...
OBJECTIVE
To compare the efficiency of multiple etiological techniques for detection of infections in wild mice, so as to provide technical supports to assessment of schistosomiasis transmission risk.
METHODS
Wild mice were captured with baited traps at night in snail-infested settings in schistosomiasis-endemic foci of Anhui Province from October to November, 2022. infections were detected in wild mice using microscopy of mouse liver tissues, microscopy of mouse mesenteric tissues, microscopy of mouse liver tissue homogenates, miracidial hatching test of mouse liver tissue homogenates, Kato-Katz technique and miracidial hatching test of mouse stool samples alone and in combinations. Identification of eggs or miracidia by any of these six assays was defined as an infection. The sensitivity of six assays alone or in combinations was compared for detection of infections in wild mice.
RESULTS
A total of 1 703 wild mice were captured, with 366 wild mice detected positive for (21.49%). There were significant differences in the prevalence of infections in wild mice by six assays ( = 529.33, < 0.001) and in the sensitivity of six assays for detection of infections in wild mice (χ = 527.78, < 0.001). In addition, the combination of microscopy of mouse liver tissues and mesenteric tissues, combination of microscopy of mouse liver tissues and liver tissue homogenates and combination of microscopy of mouse liver tissues, microscopy of mesenteric tissues, microscopy of liver tissue homogenates and Kato-Katz technique showed 86.61%, 87.16% and 97.27% sensitivities for detection of infections in wild mice, respectively.
CONCLUSIONS
Diverse etiological assays show various efficiencies for detection of infections in wild mice. Combination of microscopy of mouse liver tissues and microscopy of mesenteric tissues, and combination of microscopy of mouse liver tissues and microscopy of liver tissue homogenates are potential approaches for field detection of infections in wild mice.
Topics: Animals; Mice; Schistosomiasis japonica; Schistosoma japonicum; Schistosomiasis; Feces; Snails
PubMed: 38413018
DOI: 10.16250/j.32.1374.2023076 -
Tropical Medicine and Infectious Disease Feb 2024We established a mouse model of infection in order to study the effects of the infection on hepatocyte autophagy and apoptosis. We also stimulated HepG2 cells with...
We established a mouse model of infection in order to study the effects of the infection on hepatocyte autophagy and apoptosis. We also stimulated HepG2 cells with soluble egg antigens (SEA) in vitro. At two, four, and six weeks post-infection, quantitative real-time PCR and Western blot (WB) were used to detect liver expression levels of autophagy and apoptosis-related proteins. HepG2 cells were treated with different concentrations of SEA. The changes in the levels of autophagy-related proteins and HepG2 cell apoptosis were detected. The , , , and mRNA levels were significantly lower at four and six weeks after infection than those in the uninfected group. At four and six weeks following infection, the levels of Beclin1, LC3BII/I, Atg7, and p62 proteins were considerably lower than those in the uninfected group. The protein levels of pro-apoptotic Bax and cleaved caspase 3 and fibrosis-related proteins α-SMA and collagen 3 in the liver post-infection were significantly higher than those in uninfected mice. HepG2 cells stimulated with SEA showed decreased levels of Beclin1, p62, and Atg7 proteins and significantly increased apoptosis rates. The findings demonstrated that following infection with , mice's liver fibrosis worsened, hepatic autophagy was suppressed, and hepatocyte apoptosis was encouraged.
PubMed: 38393131
DOI: 10.3390/tropicalmed9020042 -
Parasites & Vectors Feb 2024Timely diagnosis of Toxoplasma gondii infection is necessary to prevent and control toxoplasmosis transmission. The gold immunochromatographic assay (GICA) is a means of...
BACKGROUND
Timely diagnosis of Toxoplasma gondii infection is necessary to prevent and control toxoplasmosis transmission. The gold immunochromatographic assay (GICA) is a means of rapidly detecting pathogen in samples. GICA-based diagnostic methods have been developed to accurately detect pathogens with high sensitivity and specificity, and their application in T. gondii diagnosis is expected to yield good results.
METHODS
Colloidal gold test strips were produced using T. gondii C-terminal truncated apical membrane antigen 1 (AMA1C). Colloidal gold-AMA1C and colloidal gold-murine protein conjugate were synthesized under optimal conditions. A nitrocellulose membrane was treated with AMA1C and goat anti-mouse antibody as the test line and control line, respectively. In total, 90 cat serum samples were tested using AMA1C-GICA and a commercial enzyme linked immunosorbent assay (ELISA) kit. The GICA results were digitally displayed using a portable colloidal gold immunochromatographic test strip analyzer (HMREADER). The sensitivity, specificity, and stability of AMA1C-GICA were assessed, and this was then used to examine clinical samples, including 203 human sera, 266 cat sera, and 81 dog sera.
RESULTS
AMA1C-GICA had a detection threshold of 1:32 for T. gondii-positive serum. The GICA strips specifically detected T. gondii antibodies and exhibited no reactivity with Plasmodium vivax, Paragonimus kellicotti, Schistosoma japonicum, Clonorchis sinensis, and Schistosoma mansoni. Consequently, 15 (16.7%) positive samples were detected using the AMA1C-GICA and commercial ELISA kits for each of the assays. The receiver-operating characteristic curve showed that GICA had a relative sensitivity of 85.3% and specificity of 92%, with an area under the curve of 98%. After analyzing clinical samples using HMREADER, 1.2%-23.4% of these samples were found to be positive for T. gondii.
CONCLUSIONS
This study presents a novel assay that enables timely and efficient detection of serum antibodies against T. gondii, thereby allowing for its early clinical diagnosis. Furthermore, the integration of digital detection using HMREADER can enhance the implementation of GICA.
Topics: Mice; Animals; Dogs; Humans; Chromatography, Affinity; Sensitivity and Specificity; Immunoassay; Toxoplasmosis; Enzyme-Linked Immunosorbent Assay; Antibodies, Helminth; Gold Colloid; Toxoplasma
PubMed: 38389080
DOI: 10.1186/s13071-024-06180-1