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BMC Immunology Jan 2024Despite the functions of TLRs in the parasitic infections have been extensively reported, few studies have addressed the role of TLR3 in the immune response to...
BACKGROUND
Despite the functions of TLRs in the parasitic infections have been extensively reported, few studies have addressed the role of TLR3 in the immune response to Schistosoma japonicum infections. The aim of this study was to investigate the properties of TLR3 in the liver of C57BL/6 mice infected by S. japonicum.
METHODS
The production of TLR3 cells in CD4T cells (CD4CD3), CD8T cells (CD8CD3), γδT cells (γδTCRCD3), NKT cells (NK1.1CD3), B cells (CD19CD3), NK (NK1.1CD3) cells, MDSC (CD11bGr1), macrophages (CD11bF4/80), DCs (CD11cCD11b) and neutrophils (CD11b Ly6g) were assessed by flow cytometry. Sections of the liver were examined by haematoxylin and eosin staining in order to measure the area of granulomas. Hematological parameters including white blood cell (WBC), red blood cell (RBC), platelet (PLT) and hemoglobin (HGB) were analyzed. The levels of ALT and AST in the serum were measured using biochemical kits. The relative titers of anti-SEA IgG and anti-SEA IgM in the serum were measured by enzyme-linked immunosorbent assay (ELISA). CD25, CD69, CD314 and CD94 molecules were detected by flow cytometry.
RESULTS
Flow cytometry results showed that the expression of TLR3 increased significantly after S. japonicum infection (P < 0.05). Hepatic myeloid and lymphoid cells could express TLR3, and the percentages of TLR3-expressing MDSC, macrophages and neutrophils were increased after infection. Knocking out TLR3 ameliorated the damage and decreased infiltration of inflammatory cells in infected C57BL/6 mouse livers.,The number of WBC was significantly reduced in TLR3 KO-infected mice compared to WT-infected mice (P < 0.01), but the levels of RBC, platelet and HGB were significantly increased in KO infected mice. Moreover, the relative titers of anti-SEA IgG and anti-SEA IgM in the serum of infected KO mice were statistically decreased compared with the infected WT mice. We also compared the activation-associated molecules expression between S.japonicum-infected WT and TLR3 KO mice.
CONCLUSIONS
Taken together, our data indicated that TLR3 played potential roles in the context of S. japonicum infection and it may accelerate the progression of S. japonicum-associated liver pathology.
Topics: Animals; Mice; Schistosoma japonicum; Toll-Like Receptor 3; Mice, Inbred C57BL; Immunoglobulin G; Immunoglobulin M
PubMed: 38172683
DOI: 10.1186/s12865-023-00586-9 -
Heliyon Dec 2023Rapid diagnosis of urogenital schistosomiasis caused by requires an accurate and timely assay, especially for low-intensity infection cases and in non-endemic areas....
Rapid diagnosis of urogenital schistosomiasis caused by requires an accurate and timely assay, especially for low-intensity infection cases and in non-endemic areas. The mitochondrial cytochrome oxidase 1 (cox1) gene fragment of was selected as detection target as this short fragment, which can be rapidly sequenced and yet possess good diagnostic resolution. A pair of primers and a fluorescent probe were designed according to the principle of recombinase-aided amplification (RAA), which was subsequently optimized and applied as an -specific RAA assay. Its diagnostic performance was validated for sensitivity and specificity in comparison to microscopy-based egg counting after urine filtration. The RAA assay could detect as little as 10 copies/μL of recombinant plasmid, and no cross-reactions were observed with , , , or . This test can be conducted at 39 °C and the whole RAA reaction can be completed within 20 min. The validation of the RAA assay showed that it had 100 % consistency with urine-egg microscopy, as it does not require an elaborate reading tool, is simple to use, and should be useful for field diagnostics and point-of-care applications.
PubMed: 38144328
DOI: 10.1016/j.heliyon.2023.e23031 -
Cell Communication and Signaling : CCS Dec 2023Macrophages and neutrophils are rapidly recruited around Schistosome eggs to form granulomas. Extracellular traps (ETs) of macrophages and neutrophils are part of the...
BACKGROUND
Macrophages and neutrophils are rapidly recruited around Schistosome eggs to form granulomas. Extracellular traps (ETs) of macrophages and neutrophils are part of the pathogen clearance armamentarium of leukocytes. Schistosome eggs possess the ability to resist attack by the host's immune cells and survive by employing various immune evasion mechanisms, including the release of extracellular vesicles (EVs). However, the specific mechanisms by which Schistosome egg-derived EVs (E-EVs) evade the immune response and resist attack from macrophage and neutrophil ETs remain poorly understood. In this study, we aimed to investigate the association between E-EVs and macrophage/neutrophil ETs.
METHODS
EVs were isolated from the culture supernatant of S. japonicum eggs and treated macrophages and neutrophils with E-EVs and Sja-miR-71a. The formation of ETs was then observed. Additionally, we infected mice with S. japonicum, administered HBAAV2/9-Sja-miR-71a, and the formation of macrophage ETs (METs) and neutrophil ETs (NETs) in the livers was measured. Sema4D-knockout mice, RNA sequencing, and trans-well assay were used to clarify Sja-miR-71a in E-EVs inhibits METs and NETs formation via the Sema4D/ PPAR-γ/ IL-10 axis.
RESULTS
Our findings revealed that E-EVs were internalized by macrophages and neutrophils, leading to the inhibition of METs and NETs formation. The highly expressed Sja-miR-71a in E-EVs targeted Sema4D, resulting in the up-regulation of IL-10 and subsequent inhibition of METs and NETs formation. Sema4D knockout up-regulated IL-10 expression and inhibited the formation of METs and NETs. Furthermore, we further demonstrated that Sja-miR-71a inhibits METs and NETs formation via the Sema4D/ PPAR-γ/ IL-10 axis.
CONCLUSIONS
In summary, our findings provide new insights into the immune evasion abilities of Schistosome eggs by demonstrating their ability to inhibit the formation of METs and NETs through the secretion of EVs. This study enhances our understanding of the host-pathogen interaction and may have implications for the development of novel therapeutic approaches. Video Abstract.
Topics: Mice; Animals; Extracellular Traps; Schistosoma japonicum; Interleukin-10; Peroxisome Proliferator-Activated Receptors; Neutrophils; Extracellular Vesicles; MicroRNAs; Macrophages
PubMed: 38129877
DOI: 10.1186/s12964-023-01395-8 -
Frontiers in Oncology 2023Only a few studies have focused on the association between and human malignancy. The aim of this study was to update the prevalence rate, mortality, and 5-year overall...
BACKGROUND
Only a few studies have focused on the association between and human malignancy. The aim of this study was to update the prevalence rate, mortality, and 5-year overall survival of patients with human malignancy.
METHODS
From January 20, 2018, to January 31, 2021, 5,866 inpatients were included in the study. A total of 656 patients with malignancy were identified. Cases were stratified by gender and age groups. The cancer sites, prevalence rate, mortality, and 5-year overall survival of the patients were reported. The patients with malignancy were further divided into a non-digestive system tumor group (n = 309) and a digestive system tumor group (n = 347), including those with cancer in the esophagus, stomach, colon, rectum, liver, gallbladder, bile duct, or pancreas. Chi-squared test and odds ratio with confidence intervals were performed between these two groups.
RESULTS
Lung cancer was found the most common malignancy, accounting for 18.6% of all malignancies, followed by colorectal, stomach, liver, and gallbladder cancers. These five leading malignancies accounted for approximately 61.8% of all cases. Colorectal cancer was the leading cause of malignancy death, followed by lung, stomach, gallbladder, and liver cancers. These five leading causes of death accounted for approximately 55.6% of all death cases. Statistical significance was found in the prevalence rate between and non- patients with/without digestive system tumor (p < 0.001). The odds ratio of patients with digestive system tumors was 1.6 (95%CI: 1.4-1.9).
CONCLUSION
contributes to a significant prevalence and mortality in digestive system tumors, including colorectal, stomach, liver, and gallbladder cancers.
PubMed: 38125940
DOI: 10.3389/fonc.2023.1288197 -
Parasitology Mar 2024Schistosomiasis, a parasite infectious disease caused by , often leads to egg granuloma and fibrosis due to the inflammatory reaction triggered by egg antigens released...
Schistosomiasis, a parasite infectious disease caused by , often leads to egg granuloma and fibrosis due to the inflammatory reaction triggered by egg antigens released in the host liver. This study focuses on the role of the egg antigens CP1412 protein of (SjCP1412) with RNase activity in promoting liver fibrosis. In this study, the recombinant egg ribonuclease SjCP1412, which had RNase activity, was successfully prepared. By analysing the serum of the population, it has been proven that the anti-SjCP1412 IgG in the serum of patients with advanced schistosomiasis was moderately correlated with liver fibrosis, and SjCP1412 may be an important antigen associated with liver fibrosis in schistosomiasis. , the rSjCP1412 protein induced the human liver cancer cell line Hep G2 and liver sinusoidal endothelial cells apoptosis and necrosis and the release of proinflammatory damage-associated molecular patterns (DAMPs). In mice infected with schistosomes, rSjCP1412 immunization or antibody neutralization of SjCP1412 activity significantly reduced cell apoptosis and necroptosis in liver tissue, thereby reducing inflammation and liver fibrosis. In summary, the SjCP1412 protein plays a crucial role in promoting liver fibrosis during schistosomiasis through mediating the liver cells apoptosis and necroptosis to release DAMPs inducing an inflammatory reaction. Blocking SjCP1412 activity could inhibit its proapoptotic and necrotic effects and alleviate hepatic fibrosis. These findings suggest that SjCP1412 may be served as a promising drug target for managing liver fibrosis in schistosomiasis japonica.
Topics: Humans; Mice; Animals; Schistosomiasis japonica; Ribonucleases; Endothelial Cells; Liver Cirrhosis; Schistosoma japonicum; Liver; Inflammation
PubMed: 38105713
DOI: 10.1017/S0031182023001361 -
Parasites & Vectors Dec 2023Schistosomiasis, the second largest parasitic disease in the world after malaria, poses a significant threat to human health and causes public health issues. The disease... (Review)
Review
Exploring the immune interactions between Oncomelania hupensis and Schistosoma japonicum, with a cross-comparison of immunological research progress in other intermediate host snails.
Schistosomiasis, the second largest parasitic disease in the world after malaria, poses a significant threat to human health and causes public health issues. The disease primarily affects populations in economically underdeveloped tropical regions, earning it the title of "neglected tropical disease". Schistosomiasis is difficult to eradicate globally if medication alone is used. One of the essential elements of thorough schistosomiasis prevention and control is the management and disruption of the life cycle of intermediate host snails. The key approach to controlling the transmission of schistosomiasis is to control the intermediate hosts of the schistosome to disrupt its life cycle. We believe that approaching it from the perspective of the intermediate host's immunity could be an environmentally friendly and potentially effective method. Currently, globally significant intermediate host snails for schistosomes include Oncomelania hupensis, Biomphalaria glabrata, and Bulinus truncatus. The immune interaction research between B. glabrata and Schistosoma mansoni has a history of several decades, and the complete genome sequencing of both B. glabrata and B. truncatus has been accomplished. We have summarized the immune-related factors and research progress primarily studied in B. glabrata and B. truncatus and compared them with several humoral immune factors that O. hupensis research focuses on: macrophage migration inhibitory factor (MIF), Toll-like receptors (TLRs), and thioredoxin (Trx). We believe that continued exploration of the immune interactions between O. hupensis and Schistosoma japonicum is valuable. This comparative analysis can provide some direction and clues for further in-depth research. Comparative immunological studies between them not only expand our understanding of the immune defense responses of snails that act as intermediaries for schistosomes but also facilitate the development of more comprehensive and integrated strategies for schistosomiasis prevention and control. Furthermore, it offers an excellent opportunity to study the immune system of gastropods and their co-evolution with pathogenic organisms.
Topics: Animals; Humans; Schistosoma japonicum; Schistosomiasis; Biomphalaria; Bulinus; Schistosoma mansoni
PubMed: 38093363
DOI: 10.1186/s13071-023-06011-9 -
Veterinary Research Dec 2023Schistosomiasis is a neglected tropical disease that affects humans and animals in tropical and subtropical regions worldwide. Schistosome eggs are responsible for the...
Schistosomiasis is a neglected tropical disease that affects humans and animals in tropical and subtropical regions worldwide. Schistosome eggs are responsible for the pathogenesis and transmission of schistosomiasis, thus reducing egg production is vital for prevention and control of schistosomiasis. However, the mechanisms underlying schistosome reproduction remain unclear. Annexin proteins (ANXs) are involved in the physiological and pathological functions of schistosomes, but the specific regulatory mechanisms and roles of ANX A13 in the development of Schistosoma japonicum and host-parasite interactions remain poorly understood. Therefore, in this study, the expression profiles of SjANX A13 at different life cycle stages of S. japonicum were assessed using quantitative PCR. In addition, the expression profiles of the homolog in S. mansoni were analyzed in reference to public datasets. The results of RNA interference showed that knockdown of SjANX A13 significantly affected the development and egg production of female worms in vivo. The results of an immune protection assay showed that recombinant SjANX A13 increased production of immunoglobulin G-specific antibodies. Finally, co-culture of S. japonicum exosomes with LX-2 cells using a transwell system demonstrated that SjANX A13 is involved in host-parasite interactions via exosomes. Collectively, these results will help to clarify the roles of SjANX A13 in the development of S. japonicum and host-parasite interactions as a potential vaccine candidate.
Topics: Humans; Female; Animals; Schistosoma japonicum; Schistosomiasis; Immunoglobulin G; Reproduction; Annexins
PubMed: 38049816
DOI: 10.1186/s13567-023-01244-z -
The Journal of Biological Chemistry Jan 2024Parasitic flatworms cause various clinical and veterinary infections that impart a huge burden worldwide. The most clinically impactful infection is schistosomiasis, a...
Parasitic flatworms cause various clinical and veterinary infections that impart a huge burden worldwide. The most clinically impactful infection is schistosomiasis, a neglected tropical disease caused by parasitic blood flukes. Schistosomiasis is treated with praziquantel (PZQ), an old drug introduced over 40 years ago. New drugs are urgently needed, as while PZQ is broadly effective it suffers from several limitations including poor efficacy against juvenile worms, which may prevent it from being completely curative. An old compound that retains efficacy against juvenile worms is the benzodiazepine meclonazepam (MCLZ). However, host side effects caused by benzodiazepines preclude development of MCLZ as a drug and MCLZ lacks an identified parasite target to catalyze rational drug design for engineering out human host activity. Here, we identify a transient receptor potential ion channel of the melastatin subfamily, named TRPM, as a parasite target of MCLZ. MCLZ potently activates Schistosoma mansoni TRPM through engagement of a binding pocket within the voltage-sensor-like domain of the ion channel to cause worm paralysis, tissue depolarization, and surface damage. TRPM reproduces all known features of MCLZ action on schistosomes, including a lower activity versus Schistosoma japonicum, which is explained by a polymorphism within this voltage-sensor-like domain-binding pocket. TRPM is distinct from the TRP channel targeted by PZQ (TRPM), with both anthelmintic chemotypes targeting unique parasite TRPM paralogs. This advances TRPM as a novel druggable target that could circumvent any target-based resistance emerging in response to current mass drug administration campaigns centered on PZQ.
Topics: Animals; Humans; Anthelmintics; Benzodiazepines; Benzodiazepinones; Clonazepam; Praziquantel; Schistosoma mansoni; Schistosomiasis mansoni; TRPM Cation Channels
PubMed: 38043794
DOI: 10.1016/j.jbc.2023.105528 -
PLoS Neglected Tropical Diseases Nov 2023Schistosomiasis is one of the most important neglected tropical infectious diseases to overcome and the primary cause of its pathogenesis is ectopic maturation of the...
BACKGROUND
Schistosomiasis is one of the most important neglected tropical infectious diseases to overcome and the primary cause of its pathogenesis is ectopic maturation of the parasite eggs. Uptake of cholesteryl ester from the host high-density lipoprotein (HDL) is a key in this process in Schistosoma japonicum and CD36-related protein (CD36RP) has been identified as the receptor for this reaction. Antibody against the extracellular domain of CD36RP (Ex160) efficiently blocked the HDL cholesteryl ester uptake and the egg embryonation in vitro. However, whether Ex160 immunization could efficiently raise proper antibody responses to sufficiently block HDL cholesteryl ester uptake and the egg embryonation to protect host in vivo is very interesting but unknown.
METHODOLOGY/PRINCIPAL FINDINGS
In this study, rabbits were immunized with the recombinant Ex160 peptide (rEx160) to evaluate its anti-pathogenic vaccine potential. Immunization with rEx160 induced consistent anti-Ex160 IgG antibody and significant reduction in development of the liver granulomatosis lesions associated with suppressed intrahepatic maturation of the schistosome eggs. The immunization with rEx160 rescued reduction of serum HDL by the infection without changing its size distribution, being consistent with interference of the HDL lipid uptake by the parasites or their eggs by antibody against Ex160 in in vitro culture.
CONCLUSIONS/SIGNIFICANCE
The results demonstrated that vaccination strategy against nutritional supply pathway of the parasite is effective for reducing its pathogenesis.
Topics: Animals; Rabbits; Schistosomiasis japonica; Schistosoma japonicum; Lipoproteins, HDL; Vaccination
PubMed: 38019787
DOI: 10.1371/journal.pntd.0011749 -
BMC Medical Genomics Oct 2023Schistosoma japonicum infection is an important public health problem and the S. japonicum infection is associated with a variety of diseases, including colorectal...
Schistosoma japonicum infection is an important public health problem and the S. japonicum infection is associated with a variety of diseases, including colorectal cancer. We collected the paraffin samples of CRC patients with or without S. japonicum infection according to standard procedures. Data-Independent Acquisition was used to identify differentially expressed proteins (DEPs), protein-protein interaction (PPI) network construction, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis and machine learning algorithms (least absolute shrinkage and selection operator (LASSO) regression) were used to identify candidate genes for diagnosing CRC with S. japonicum infection. To assess the diagnostic value, the nomogram and receiver operating characteristic (ROC) curve were developed. A total of 115 DEPs were screened, the DEPs that were discovered were mostly related with biological process in generation of precursor metabolites and energy,energy derivation by oxidation of organic compounds, carboxylic acid metabolic process, oxoacid metabolic process, cellular respiration aerobic respiration according to the analyses. Enrichment analysis showed that these compounds might regulate oxidoreductase activity, transporter activity, transmembrane transporter activity, ion transmembrane transporter activity and inorganic molecular entity transmembrane transporter activity. Following the development of PPI network and LASSO, 13 genes (hsd17b4, h2ac4, hla-c, pc, epx, rpia, tor1aip1, mindy1, dpysl5, nucks1, cnot2, ndufa13 and dnm3) were filtered, and 3 candidate hub genes were chosen for nomogram building and diagnostic value evaluation after machine learning. The nomogram and all 3 candidate hub genes (hsd17b4, rpia and cnot2) had high diagnostic values (area under the curve is 0.9556). The results of our study indicate that the combination of hsd17b4, rpia, and cnot2 may become a predictive model for the occurrence of CRC in combination with S. japonicum infection. This study also provides new clues for the mechanism research of S. japonicum infection and CRC.
Topics: Humans; Animals; Coinfection; Proteomics; Schistosoma japonicum; Schistosomiasis japonica; Computational Biology; Machine Learning; Colorectal Neoplasms
PubMed: 37904220
DOI: 10.1186/s12920-023-01711-8