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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 -
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 -
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 -
PLoS Neglected Tropical Diseases Feb 2024Schistosomiasis is one of the most devastating human diseases worldwide. The disease is caused by six species of Schistosoma blood fluke; five of which cause intestinal...
Schistosomiasis is one of the most devastating human diseases worldwide. The disease is caused by six species of Schistosoma blood fluke; five of which cause intestinal granulomatous inflammation and bleeding. The current diagnostic method is inaccurate and delayed, hence, biomarker identification using metabolomics has been applied. However, previous studies only investigated infection caused by one Schistosoma spp., leaving a gap in the use of biomarkers for other species. No study focused on understanding the progression of intestinal disease. Therefore, we aimed to identify early gut biomarkers of infection with three Schistosoma spp. and progression of intestinal pathology. We infected 3 groups of mice, 3 mice each, with Schistosoma mansoni, Schistosoma japonicum or Schistosoma mekongi and collected their feces before and 1, 2, 4 and 8 weeks after infection. Metabolites in feces were extracted and identified using mass spectrometer-based metabolomics. Metabolites were annotated and analyzed with XCMS bioinformatics tool and Metaboanalyst platform. From >36,000 features in all conditions, multivariate analysis found a distinct pattern at each time point for all species. Pathway analysis reported alteration of several lipid metabolism pathways as infection progressed. Disturbance of the glycosaminoglycan degradation pathway was found with the presence of parasite eggs, indicating involvement of this pathway in disease progression. Biomarkers were discovered using a combination of variable importance for projection score cut-off and receiver operating characteristic curve analysis. Five molecules met our criteria and were present in all three species: 25-hydroxyvitamin D2, 1α-hydroxy-2β-(3-hydroxypropoxy) vitamin D3, Ganoderic acid Md, unidentified feature with m/z 455.3483, and unidentified feature with m/z 456.3516. These molecules were proposed as trans-genus biomarkers of early schistosomiasis. Our findings provide evidence for disease progression in intestinal schistosomiasis and potential biomarkers, which could be beneficial for early detection of this disease.
Topics: Mice; Humans; Animals; Schistosomiasis mansoni; Schistosomiasis; Schistosoma japonicum; Biomarkers; Early Diagnosis; Disease Progression
PubMed: 38381759
DOI: 10.1371/journal.pntd.0011966 -
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 -
Animals : An Open Access Journal From... Feb 2024Fasciolosis is a global zoonotic parasitic disease caused by infection that is particularly harmful to cattle and sheep. A biotin-streptavidin signal amplification...
The Detection of Circulating Antigen Glutathione S-Transferase in Sheep Infected with with Double-Antibody Sandwich Signal Amplification Enzyme-Linked Immunosorbent Assay.
Fasciolosis is a global zoonotic parasitic disease caused by infection that is particularly harmful to cattle and sheep. A biotin-streptavidin signal amplification ELISA (streptavidin-ELISA/SA-ELISA) based on circulating antigens can allow for the early detection of -infected animals and is suitable for batch detection. It is considered to be a better means of detecting infection than traditional detection methods. In this study, using the serum of sheep artificially infected with , the cDNA expression library of was screened, 17 immunodominant antigen genes of were obtained, and glutathione s-transferase (GST) was selected as the candidate detection antigen. Firstly, the GST cDNA sequence was amplified from , followed by the preparation of recombinant protein GST (rFhGST). Then, monoclonal and polyclonal antibodies against rFhGST were prepared using the GST protein. Afterward, the immunolocalization of the target protein in the worm was observed via confocal microscopy, and it was found that the GST protein was localized in the uterus, intestinal tract, and body surface of . Finally, a double-antibody sandwich SA-ELISA based on the detection of circulating antigens was established. There was no cross-reaction with positive sera infected with (), (), (), or (). Forty serum and fecal samples from the same batch of sheep in Nong'an County, Changchun City, Jilin Province, China were analyzed using the established detection method and fecal detection method. The positive rate of the SA-ELISA was 17.5%, and the positive rate of the fecal detection method was 15%. The detection results of this method were 100% consistent with commercial ELISA kits. A total of 152 sheep serum samples were tested in Nong'an County, Changchun City, Jilin Province, and the positive rate was 5.92%. This study laid the foundation for the development of serological detection preparations for infection based on the detection of circulating antigens.
PubMed: 38338149
DOI: 10.3390/ani14030506 -
PLoS Pathogens Jan 2024Schistosomes are flatworm parasites that undergo a complex life cycle involving two hosts. The regulation of the parasite's developmental processes relies on both coding...
Schistosomes are flatworm parasites that undergo a complex life cycle involving two hosts. The regulation of the parasite's developmental processes relies on both coding RNAs and non-coding RNAs. However, the roles of non-coding RNAs, including long non-coding RNAs (lncRNAs) in schistosomes remain largely unexplored. Here we conduct advanced RNA sequencing on male and female S. japonicum during their pairing and reproductive development, resulting in the identification of nearly 8,000 lncRNAs. This extensive dataset enables us to construct a comprehensive co-expression network of lncRNAs and mRNAs, shedding light on their interactions during the crucial reproductive stages within the mammalian host. Importantly, we have also revealed a specific lncRNA, LNC3385, which appears to play a critical role in the survival and reproduction of the parasite. These findings not only enhance our understanding of the dynamic nature of lncRNAs during the reproductive phase of schistosomes but also highlight LNC3385 as a potential therapeutic target for combating schistosomiasis.
Topics: Animals; Male; Female; Schistosoma japonicum; RNA, Long Noncoding; RNA, Antisense; Schistosomiasis; Parasites; Mammals
PubMed: 38285715
DOI: 10.1371/journal.ppat.1011949 -
Scientific Reports Jan 2024Schistosoma mekongi, a significant schistosome parasite, has various life stages, including egg, cercaria, female, and male, that play crucial roles in the complex life...
Schistosoma mekongi, a significant schistosome parasite, has various life stages, including egg, cercaria, female, and male, that play crucial roles in the complex life cycle. This study aimed to explore the microRNA (miRNA) profiles across these developmental stages to understand their potential functions and evolutionary significance, which have not been studied. Pre-processed sequencing reads of small RNA (sRNA) were obtained, and annotations were performed against the S. japonicum reference miRNA database. Results indicated marked variations in miRNA profiles across different life stages, with notable similarities observed between female and male S. mekongi. Principal Coordinate Analysis (PCoA) and unsupervised clustering revealed distinct miRNA signatures for each stage. Gene ontology (GO) analysis unveiled the potential roles of these miRNAs in various biological processes. The differential expression of specific miRNAs was prominent across stages, suggesting their involvement in crucial developmental processes. Furthermore, orthologous miRNA analysis against various worm species revealed distinct presence-absence patterns, providing insights into the evolutionary relationships of these miRNAs. In conclusion, this comprehensive investigation into the miRNA profiles of S. mekongi offers valuable insights into the functional and evolutionary aspects of miRNAs in schistosome biology.
Topics: Animals; Male; Female; Schistosoma japonicum; MicroRNAs; Life Cycle Stages; RNA, Helminth
PubMed: 38281987
DOI: 10.1038/s41598-024-52835-5 -
Tropical Medicine and Infectious Disease Dec 2023Snail control to complement mass drug administration is being promoted by the World Health Organization for schistosomiasis control. , the snail intermediate host of in...
From Perpetual Wetness to Soil Chemistry: Enumerating Environmental and Physicochemical Factors Favoring Snail Presence in the Municipality of Gonzaga, Cagayan, Philippines.
Snail control to complement mass drug administration is being promoted by the World Health Organization for schistosomiasis control. , the snail intermediate host of in the Philippines, has a very focal distribution; thus, scrutinizing baseline data and parameters affecting this distribution is very crucial. In this study in Gonzaga, Cagayan, Philippines, snail habitats were surveyed, and the various factors affecting the existence of the snails were determined. Malacological surveys and the mapping of sites of perpetual wetness in five endemic and five neighboring non-endemic barangays were conducted. Environmental and physicochemical factors were also examined. Maps of both snail and non-snail sites were generated. Of the fifty sites surveyed, were found in twelve sites, and two sites yielded snails that were infected with cercariae. Factors such as silty loam soil, proximity to a snail site, water ammonia, and soil attributes (organic matter, iron, and pH) are all significantly associated with the presence of snails. In contrast, types of habitats, temperatures, and soil aggregation have no established association with the existence of snails. Mapping snail sites and determining factors favoring snail presence are vital to eliminating snails. These approaches will significantly maximize control impact and minimize wasted efforts and resources, especially in resource-limited schistosomiasis endemic areas.
PubMed: 38251207
DOI: 10.3390/tropicalmed9010009