The European Nucleotide Archive in 2023.

The European Nucleotide Archive (ENA; https://www.ebi.ac.uk/ena) is maintained by the European Molecular Biology Laboratory's European Bioinformatics Institute (EMBL-EBI). The ENA is one of the three members of the International Nucleotide Sequence Database Collaboration (INSDC). It serves the bioinformatics community worldwide via the submission, processing, archiving and dissemination of sequence data. The ENA supports data types ranging from raw reads, through alignments and assemblies to functional annotation. The data is enriched with contextual information relating to samples and experimental configurations. In this article, we describe recent progress and improvements to ENA services. In particular, we focus upon three areas of work in 2023: FAIRness of ENA data, pandemic preparedness and foundational technology. For FAIRness, we have introduced minimal requirements for spatiotemporal annotation, created a metadata-based classification system, incorporated third party metadata curations with archived records, and developed a new rapid visualisation platform, the ENA Notebooks. For foundational enhancements, we have improved the INSDC data exchange and synchronisation pipelines, and invested in site reliability engineering for ENA infrastructure. In order to support genomic surveillance efforts, we have continued to provide ENA services in support of SARS-CoV-2 data mobilisation and have adapted these for broader pathogen surveillance efforts.

Mask exhibits trxG-like behavior and associates with H3K27ac marked chromatin.

The Trithorax group (trxG) proteins counteract the repressive effect of Polycomb group (PcG) complexes and maintain transcriptional memory of active states of key developmental genes. Although chromatin structure and modifications appear to play a fundamental role in this process, it is not clear how trxG prevents PcG-silencing and heritably maintains an active gene expression state. Here, we report a hitherto unknown role of Drosophila Multiple ankyrin repeats single KH domain (Mask), which emerged as one of the candidate trxG genes in our reverse genetic screen. The genome-wide binding profile of Mask correlates with known trxG binding sites across the Drosophila genome. In particular, the association of Mask at chromatin overlaps with CBP and H3K27ac, which are known hallmarks of actively transcribed genes by trxG. Importantly, Mask predominantly associates with actively transcribed genes in Drosophila. Depletion of Mask not only results in the downregulation of trxG targets but also correlates with diminished levels of H3K27ac. The fact that Mask positively regulates H3K27ac levels in flies was also found to be conserved in human cells. Strong suppression of Pc mutant phenotype by mutation in mask provides physiological relevance that Mask contributes to the anti-silencing effect of trxG, maintaining expression of key developmental genes. Since Mask is a downstream effector of multiple cell signaling pathways, we propose that Mask may connect cell signaling with chromatin mediated epigenetic cell memory governed by trxG.

The European Nucleotide Archive in 2022.

The European Nucleotide Archive (ENA; https://www.ebi.ac.uk/ena), maintained by the European Molecular Biology Laboratory's European Bioinformatics Institute (EMBL-EBI), offers those producing data an open and supported platform for the management, archiving, publication, and dissemination of data; and to the scientific community as a whole, it offers a globally comprehensive data set through a host of data discovery and retrieval tools. Here, we describe recent updates to the ENA's submission and retrieval services as well as focused efforts to improve connectivity, reusability, and interoperability of ENA data and metadata.

Safety and adverse events of EUS-guided gallbladder drainage using lumen-apposing metal stents and percutaneous cholecystostomy tubes: a systematic review and meta-analysis.

BACKGROUND AND AIMS: EUS-guided gallbladder drainage using lumen-apposing metal stents (EUS-GBD-LAMSs) and percutaneous cholecystostomy for gallbladder drainage (PTGBD) are the alternative treatment modalities in high-risk surgical patients with acute cholecystitis (AC). The aim of this study was to compare the safety of these procedures for AC in surgically suboptimal candidates. METHODS: Six studies compared the 2 groups' early, delayed, and overall adverse events; they also compared length of hospital stay, re-interventions, and re-admissions rate. A random effect model calculated odds ratios (ORs) with a 95% confidence interval (CI). RESULTS: The 2 groups had similar early adverse events; however, EUS-GBD-LAMS was associated with a lower rate of delayed (OR, .21; 95% CI, .07-.61; P ≤ .01) and overall (OR, .43; 95% CI, .30-.61; P ≤ .01) adverse events. Patients with EUS-GBD-LAMSs had a shorter hospital stay than PTGBD. CONCLUSIONS: EUS-GBD-LAMS is a safer option than PTGBD and is associated with a shorter hospital stay in nonsurgical candidates with AC.

Adjuvant Radiofrequency Ablation Along With Stenting Versus Stenting Alone for Biliary Tree Drainage in Patients With Malignant Biliary Strictures: A Systemic Review and Meta-analysis.

OBJECTIVE: This metanalysis aims to assess the efficacy and safety of biliary stenting along with radiofrequency ablation compared with stents alone to treat malignant biliary obstruction (MBO) due to extrahepatic biliary strictures secondary to cholangiocarcinoma, pancreatic cancer, and metastatic cancer. METHODS: A systemic search of major databases through April 2022 was done. All original studies were included comparing radiofrequency ablation with stenting versus stenting alone for treating malignant biliary strictures. The primary outcomes of interest were the difference in the mean stent patency and overall survival (OS) days between the 2 groups. The secondary outcome was to compare the adverse events of the 2 groups. The mean difference in the stent patency and OS days was pooled by using a random-effect model. We calculated the odds ratio to compare the adverse events between the 2 groups. RESULTS: A total of 13 studies with 1339 patients were identified. The pooled weighted mean difference in stent patency was 43.50 days (95% CI, 25.60-61.41), favoring the RFA plus stenting. Moreover, the pooled weighted mean difference in OS was 90.53 days (95% CI, 49.00-132.07), showing improved survival in the RFA group. Our analysis showed no statistically significant difference in adverse events between the 2 groups OR 1.13 (95% CI, 0.90-1.42). CONCLUSION: Our analysis showed that RFA, along with stent, is safe and is associated with improved stent patency and overall patient survival in malignant biliary strictures. More robust prospective studies should assess this association further.

Discovery of Novel Small Molecule Dual Inhibitor Targeting Toll-Like Receptors 7 and 9.

The aberrant secretion of proinflammatory cytokines by immune cells is the principal cause of inflammatory diseases, such as systemic lupus erythematosus and rheumatoid arthritis. Toll-like receptor 7 (TLR7) and TLR9, sequestered to the endosomal compartment of dendritic cells and macrophages, are closely associated with the initiation and progression of these diseases. Therefore, the development of drugs targeting dysregulated endosomal TLRs is imperative to mitigate systemic inflammation. Here, we applied the principles of computer-aided drug discovery to identify a novel low-molecular-weight compound, TLR inhibitory compound 10 (TIC10), and its potent derivative (TIC10g), which demonstrated dual inhibition of TLR7 and TLR9 signaling pathways. Compared to TIC10, TIC10g exhibited a more pronounced inhibition of the TLR7- and TLR9-mediated secretion of the proinflammatory cytokine tumor necrosis factor-α in a mouse macrophage cell line and mouse bone marrow dendritic cells in a concentration-dependent manner. While TIC10g slightly prevented TLR3 and TLR8 activation, it had no impact on cell surface TLRs (TLR1/2, TLR2/6, TLR4, or TLR5), indicating its selectivity for TLR7 and TLR9. Additionally, mechanistic studies suggested that TIC10g interfered with TLR9 activation by CpG DNA and suppressed downstream pathways by directly binding to TLR9. Western blot analysis revealed that TIC10g downregulated the phosphorylation of the p65 subunit of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinases (MAPKs), including extracellular-signal-regulated kinase, p38-MAPK, and c-Jun N-terminal kinase. These findings indicate that the novel ligand, TIC10g, is a specific dual inhibitor of endosomal TLRs (TLR7 and TLR9), disrupting MAPK- and NF-κB-mediated proinflammatory gene expression.

The European Nucleotide Archive in 2021.

The European Nucleotide Archive (ENA, https://www.ebi.ac.uk/ena), maintained at the European Molecular Biology Laboratory's European Bioinformatics Institute (EMBL-EBI) provides freely accessible services, both for deposition of, and access to, open nucleotide sequencing data. Open scientific data are of paramount importance to the scientific community and contribute daily to the acceleration of scientific advance. Here, we outline the major updates to ENA's services and infrastructure that have been delivered over the past year.

Artificial intelligence-enhanced electrocardiography for accurate diagnosis and management of cardiovascular diseases.

Electrocardiography (ECG), improved by artificial intelligence (AI), has become a potential technique for the precise diagnosis and treatment of cardiovascular disorders. The conventional ECG is a frequently used, inexpensive, and easily accessible test that offers important information about the physiological and anatomical state of the heart. However, the ECG can be interpreted differently by humans depending on the interpreter's level of training and experience, which could make diagnosis more difficult. Using AI, especially deep learning convolutional neural networks (CNNs), to look at single, continuous, and intermittent ECG leads that has led to fully automated AI models that can interpret the ECG like a human, possibly more accurately and consistently. These AI algorithms are effective non-invasive biomarkers for cardiovascular illnesses because they can identify subtle patterns and signals in the ECG that may not be readily apparent to human interpreters. The use of AI in ECG analysis has several benefits, including the quick and precise detection of problems like arrhythmias, silent cardiac illnesses, and left ventricular failure. It has the potential to help doctors with interpretation, diagnosis, risk assessment, and illness management. Aside from that, AI-enhanced ECGs have been demonstrated to boost the identification of heart failure and other cardiovascular disorders, particularly in emergency department settings, allowing for quicker and more precise treatment options. The use of AI in cardiology, however, has several limitations and obstacles, despite its potential. The effective implementation of AI-powered ECG analysis is limited by issues such as systematic bias. Biases based on age, gender, and race result from unbalanced datasets. A model's performance is impacted when diverse demographics are inadequately represented. Potentially disregarded age-related ECG variations may result from skewed age data in training sets. ECG patterns are affected by physiological differences between the sexes; a dataset that is inclined toward one sex may compromise the accuracy of the others. Genetic variations influence ECG readings, so racial diversity in datasets is significant. Furthermore, issues such as inadequate generalization, regulatory barriers, and interpretability concerns contribute to deployment difficulties. The lack of robustness in models when applied to disparate populations frequently hinders their practical applicability. The exhaustive validation required by regulatory requirements causes a delay in deployment. Difficult models that are not interpretable erode the confidence of clinicians. Diverse dataset curation, bias mitigation strategies, continuous validation across populations, and collaborative efforts for regulatory approval are essential for the successful deployment of AI ECG in clinical settings and must be undertaken to address these issues. To guarantee a safe and successful deployment in clinical practice, the use of AI in cardiology must be done with a thorough understanding of the algorithms and their limits. In summary, AI-enhanced electrocardiography has enormous potential to improve the management of cardiovascular illness by delivering precise and timely diagnostic insights, aiding clinicians, and enhancing patient outcomes. Further study and development are required to fully realize AI's promise for improving cardiology practices and patient care as technology continues to advance.

ELIXIR biovalidator for semantic validation of life science metadata.

SUMMARY: To advance biomedical research, increasingly large amounts of complex data need to be discovered and integrated. This requires syntactic and semantic validation to ensure shared understanding of relevant entities. This article describes the ELIXIR biovalidator, which extends the syntactic validation of the widely used AJV library with ontology-based validation of JSON documents. AVAILABILITY AND IMPLEMENTATION: Source code: https://github.com/elixir-europe/biovalidator, Release: v1.9.1, License: Apache License 2.0, Deployed at: https://www.ebi.ac.uk/biosamples/schema/validator/validate. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Endoscopic therapy for gastroesophageal reflux disease: where are we, where are we going?

PURPOSE OF REVIEW: Gastroesophageal reflux disease (GERD) is the most common chronic condition with increasing prevalence in the Western world. Despite medical therapy, a considerable proportion of patients continue to experience symptoms, thus fueling the demand for minimally invasive GERD treatment options. This review will assess the currently available endoscopic approaches by analyzing their outcomes data, indication for use and limitations. RECENT FINDINGS: With increasing evidence of the safety and efficacy of endoscopic therapies, recent guidelines and consensus society documents have updated their recommendations for the endoscopic treatment of GERD. In this review, we have comprehensively assessed the current landscape of endoscopic approaches for the treatment of GERD and provided insight into future directions. SUMMARY: Endoscopic therapies for GERD show promise as new treatments emerge and existing therapies evolve into safer and more reproducible options. They are well positioned to cater to a large subset of the population suffering from chronic condition of GERD.

Short-term outcomes after peroral endoscopic myotomy, Heller myotomy, and pneumatic dilation in patients with achalasia: a nationwide analysis.

BACKGROUND AND AIMS: Peroral endoscopic myotomy (POEM), laparoscopic Heller myotomy (LHM), and pneumatic dilation (PD) are the most common modalities for management of achalasia. Our study aimed to directly compare their short-term outcomes and safety profile in a hospitalized cohort in the United States. METHODS: The National Readmission Database (2016-2019) was queried using International Classification of Diseases, Tenth Revision, Clinical Modification codes to identify a cohort of inpatient admissions who underwent POEM, LHM, or PD. Baseline demographic variables, resource utilization, periprocedural outcomes, and 30-day readmissions were analyzed. A univariate and multivariate logistic regression model was used to compare odds of readmission with POEM as a reference. RESULTS: LHM was the most performed procedure (n = 9710) as compared with PD (n = 2453) and POEM (n = 1911). Patients undergoing PD were older with a higher Charlson Comorbidity Index. The 30-day readmission rate was 4.3%, 3.9%, and 12.6% for POEM, LHM, and PD, respectively. Compared with POEM, the adjusted odds of readmission for PD was 2.42 (95% confidence interval, 1.56-3.75). There was no statistically significant difference in odds of readmission for LHM (.91; 95% confidence interval, .62-1.33) compared with POEM. Within the 30-day readmitted population, 13.1% of PD and 3.4% of LHM patients required achalasia-related procedural intervention. The rate of bleeding (4.3%), blood transfusion (2.3%), and mortality were higher (1.1%) in PD as compared with POEM and LHM. CONCLUSIONS: In the United States, the risk of readmission and resource utilization are higher in patients with achalasia undergoing PD. The outcomes are comparable between POEM and LHM, but there is a significant difference between the utilization of these myotomy procedures.

Impact of second-generation transoral incisionless fundoplication on atypical GERD symptoms: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Transoral incisionless fundoplication (TIF) using the EsophyX device (EndoGastric Solutions, Inc, Redmond, Wash, USA) is a minimally invasive endoscopic fundoplication technique. Our study aimed to assess the efficacy of TIF for atypical GERD symptoms in patients with chronic or refractory GERD. METHODS: A systematic search of 4 major databases was performed. All original studies assessing atypical GERD using a validated symptom questionnaire (the reflux symptom index [RSI]) were included. The RSI score was assessed before and after TIF at a 6- and 12-month follow-up. Data on technical success rate, adverse events, proton pump inhibitor (PPI) use, and patient satisfaction were also collected. Only TIF procedures currently in practice using the EsophyX device (ie, TIF 2.0) and TIF with concomitant hiatal hernia repair were included in the review. RESULTS: Ten studies (564 patients) were included. At the 6- and 12- month follow-up, there was a mean reduction of 15.72 (95% confidence interval, 12.15-19.29) and 14.73 (95% confidence interval, 11.74-17.72) points, respectively, in the RSI score post-TIF, with a technical success rate of 99.5% and a pooled adverse event rate of 1%. At both time intervals, more than two-thirds of the patients were satisfied with their health condition and roughly three-fourths of the patients were off daily PPIs. CONCLUSIONS: Our study shows that TIF using the EsophyX device is safe and effective in reducing atypical GERD symptoms at 6 and 12 months of follow-up. It improves patient-centered outcomes and can be a minimally invasive therapeutic option for patients suffering from atypical GERD symptoms on chronic medical therapy.

The European Nucleotide Archive in 2020.

The European Nucleotide Archive (ENA; https://www.ebi.ac.uk/ena), provided by the European Molecular Biology Laboratory's European Bioinformatics Institute (EMBL-EBI), has for almost forty years continued in its mission to freely archive and present the world's public sequencing data for the benefit of the entire scientific community and for the acceleration of the global research effort. Here we highlight the major developments to ENA services and content in 2020, focussing in particular on the recently released updated ENA browser, modernisation of our release process and our data coordination collaborations with specific research communities.

Autoimmune Neuroinflammatory Diseases: Role of Interleukins.

Autoimmune neuroinflammatory diseases are a group of disorders resulting from abnormal immune responses in the nervous system, causing inflammation and tissue damage. The interleukin (IL) family of cytokines, especially IL-1, IL-6, and IL-17, plays a critical role in the pathogenesis of these diseases. IL-1 is involved in the activation of immune cells, production of pro-inflammatory cytokines, and promotion of blood-brain barrier breakdown. IL-6 is essential for the differentiation of T cells into Th17 cells and has been implicated in the initiation and progression of neuroinflammation. IL-17 is a potent pro-inflammatory cytokine produced by Th17 cells that plays a crucial role in recruiting immune cells to sites of inflammation. This review summarizes the current understanding of the roles of different interleukins in autoimmune neuroinflammatory diseases, including multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease, neuromyelitis optica, and autoimmune encephalitis, and discusses the potential of targeting ILs as a therapeutic strategy against these diseases. We also highlight the need for further research to better understand the roles of ILs in autoimmune neuroinflammatory diseases and to identify new targets for treating these debilitating diseases.

Spatial soil loss prediction impacted by long-term land use/land cover change: a case study of Swat District.

Soil erosion is a destructive consequence of land degradation caused by deforestation, improper farming practices, overgrazing, and urbanization. This irreversible effect negatively impacts the limited renewable soil resource, causing soil truncation, reduced fertility, and unstable slopes. To address the anticipation of erosion modulus resulting from long-term land use and land cover (LULC) changes, a study was conducted in the Swat District of Khyber Pakhtunkhwa (Kpk), Pakistan. The study aimed to predict and evaluate soil erosion concerning these changes using remote sensing (RS), geographic information systems (GIS), and the Revised Universal Soil Loss Equation (RUSLE) model. We also evaluated the impact of the Billion Tree Tsunami Project (BTTP) on soil erosion in the region. Model inputs, such as rainfall erosivity factor, topography factor, land cover and management factor, and erodibility factor, were used to calculate soil erosion. The results revealed that significant soil loss occurred under 2001, 2011, and 2021 LULC conditions, accounting for 67.26%, 61.78%, and 65.32%, falling within the category of low erosion potential. The vulnerable topographical features of the area indicated higher erosion modulus. The maximum soil loss rates observed in 2001, 2011, and 2021 were 80 t/ha-1/year-1, 120 t/ha-1/year-1, and 96 t/ha-1/year-1, respectively. However, the observed reduction in soil loss in 2021 as compared to 2001 and 2011 suggests a positive influence of the BTTP on soil conservation efforts. This study underscores the potential of afforestation initiatives like the BTTP in mitigating soil erosion and highlights the significance of environmental conservation programs in regions with vulnerable topography.

Quantifying irrigation water demand and supply gap using remote sensing and GIS in Multan, Pakistan.

Human interventions and rapid changes in land use adversely affect the adequate distribution of water resources. A research study was conducted to quantify the gap between demand and supply for irrigation water in Multan, Pakistan, which may lead to sustainable water management. Two remotely sensed images (Landsat 8 OLI and Landsat 5 TM) were downloaded for the years 2010 and 2020, and supervised classification method was performed for the selected land use land cover (LULC) classes and basic framework. During the evaluation, the kappa coefficient was found in the ranges of 0.83-0.85, and overall accuracy was found to be more than 80% which indicated a substantial agreement between the classified maps and the ground truth data for both years and seasons. The LULC maps showed that urbanization has increased by 49% during the last decade (2010-2020). Reduction in planting areas for wheat (9%), cotton (24%), and orchards (46%) was observed. An increase in planting areas for rice (92%) and sugarcane (63%) was observed. The changing LULC pattern may be related to variation in water demand and supply for irrigation. The irrigation water demand has decreased by 370.2 Mm3 from 2010 to 2020, due to the reduction in agricultural land and an increase in urbanization. Available irrigation water supply (canals/rainfall) was estimated as 2432 Mm3 for the year 2020 which was 26% less than that of total irrigation water demand (3281 Mm3). The findings also provide the database for sustainable water management and equitable distribution of water in the region.

Em14-3-3 delivered by PLGA and chitosan nanoparticles conferred improved protection in chicken against Eimeria maxima.

Eimeria maxima (E. maxima) are an intracellular apicomplexan protozoan that causes intestinal coccidiosis in chickens. The purpose of this research was to develop a novel delivery approach for recombinant E. maxima (rEm) 14-3-3 antigen to elicit enhanced immunogenic protection using poly (D, L-lactide-co-glycolide) (PLGA) and chitosan (CS) nanoparticles (NPs) against E. maxima challenge. The morphologies of prepared antigen-loaded NPs (PLGA/CS-rEm14-3-3 NPs) were visualized by a scanning electron microscope. The rEm14-3-3 and PLGA/CS-rEm14-3-3 NPs-immunized chicken-induced changes of serum cytokines, IgY-antibody level, and T-lymphocyte subsets and protective efficacies against E. maxima challenge were evaluated. The results revealed that encapsulated rEm14-3-3 in PLGA and CS NPs presented spherical morphology with a smooth surface. The chickens immunized with only rEm14-3-3 and PLGA/CS-rEm14-3-3 NPs elicited a significant (p<0.05) higher level of IFN-γ cytokine, stimulated the proportions of CD4+/CD3+, CD8+/CD3+ T-cells, and provoked sera IgY-antibody immune response compared to control groups (PBS, pET-32a, PLGA, and CS). Whereas, PLGA-rEm14-3-3 NP-immunized chicken provoked a higher level of IFN- γ production and IgY-antibody response rather than CS-rEm14-3-3 and bare antigen, relatively. The animal experiment results ratified that PLGA-rEm14-3-3 NP-immunized chicken significantly alleviated the relative body weight gain (%), decreased lesion score, and enhanced oocyst decrease ratio compared to CS-rEm14-3-3 NPs and only rEm14-3-3. The anti-coccidial index of the chicken vaccinated with the PLGA-rEm14-3-3 NPs was (180.1) higher than that of the Cs-rEm14-3-3 NPs (167.4) and bare antigen (165.9). Collectively, our statistics approved that PLGA NPs might be an efficient antigen carrier system (Em14-3-3) to act as a nanosubunit vaccine that can improve protective efficacies in chicken against E. maxima challenge.

Toll-like Receptor Mediation in SARS-CoV-2: A Therapeutic Approach.

The innate immune system facilitates defense mechanisms against pathogen invasion and cell damage. Toll-like receptors (TLRs) assist in the activation of the innate immune system by binding to pathogenic ligands. This leads to the generation of intracellular signaling cascades including the biosynthesis of molecular mediators. TLRs on cell membranes are adept at recognizing viral components. Viruses can modulate the innate immune response with the help of proteins and RNAs that downregulate or upregulate the expression of various TLRs. In the case of COVID-19, molecular modulators such as type 1 interferons interfere with signaling pathways in the host cells, leading to an inflammatory response. Coronaviruses are responsible for an enhanced immune signature of inflammatory chemokines and cytokines. TLRs have been employed as therapeutic agents in viral infections as numerous antiviral Food and Drug Administration-approved drugs are TLR agonists. This review highlights the therapeutic approaches associated with SARS-CoV-2 and the TLRs involved in COVID-19 infection.

Appraisal of the pharmacokinetic profile, histopathology and stability studies of a fast dissolving oral film based on natural polysaccharide.

The present research is designed to evaluate the pharmacokinetic profile, histological evaluation, and stability studies of an orodispersible film (ODF) of tizanidine (TZ) and meloxicam (MX) prepared from a natural polysaccharide, i.e., xanthan gum. In vivo release study of TZ and MX was performed in rabbits and results indicated the better pharmacokinetics parameters and improved the oral bioavailability when compared to the oral aqueous suspension and solution of TZ and MX, respectively. The intermediate stability studies were performed at 30±2°C and 65±5% RH, whereas, the accelerated stability studies were carried out at 40±2°C and 75±5% RH, respectively for the duration of six months and results indicated that the ODF was stable for six months without any substantial difference in essential physico-chemical parameters, mechanical attributes, and morphological constraints. The toxicity profile of ODF was determined through histopathology of vital organs after administering the ODF to the rabbits. Histopathology revealed that the tissues of all vital organs are normal and did not exhibit any abnormalities, lesions, or hemorrhage. Therefore, the ODF prepared from xanthan gum exhibited a non-toxic and stable formulation with a better pharmacokinetics profile of MX and TZ.

Actin-depolymerizing factor from Eimeria tenella promotes immunogenic function of chicken dendritic cells.

Dendritic cells play a crucial role in inducing antigen-specific immunity to pathogens. During host-parasite interaction, host immune response to the parasite molecules is considered essential for recognizing novel antigens for control strategies. Therefore, in the present study, chicken dendritic cells (DCs) (ChDCs), derived from spleens were used to evaluate their capacity to proliferate and differentiate autologous T lymphocytes in response to actin-depolymerizing factor from Eimeria tenella (EtADF). Immunoblot analysis showed that recombinant EtADF protein (rEtADF) was able to interact with rat anti-rEtADF antibodies. The immunofluorescence test confirmed rEtADF binding on ChDCs surface. Flow cytometric analysis revealed that phenotypes for MHCII, CD1.1, CD11c, CD80, and CD86 were increased in ChDCs after rEtADF treatment. qRT-PCR results indicated that ChDCs triggered TLR signaling in response to rEtADF, and suppressed Wnt signaling. Transcript levels of CD83, CCL5, and CCR7 in ChDCs were improved following rEtADF treatment. In addition, rEtADF promoted DC-directed T cell proliferation and differentiation of naïve T cells into CD3+/CD4+ T cells in DC/T cell co-incubation system. Cytokine analysis of rEtADF-pulsed ChDCs showed increased levels of IL-12 and IFN-γ, while IL-10 and TGF-ß remained unchanged. Moreover, rEtADF-treated ChDCs enhanced production of IFN-γ when incubated with T cells, and IL-4 secretion remained unchanged. Our findings indicted that rEtADF could facilitate the polarization of Th1 immune cells by triggering both host DCs and T cells. Our findings provide useful insights into future work aimed at anticoccidial vaccine strategies.