Find research datasets worth reusing

opencc-byApr 2023View details →

Metabolome analysis and immunity of Phlomis purpurea against Phytophthora cinnamomi

Abstract   Phlomis purpurea is spontaneous in the southern Iberian Peninsula namely in cork oak (Quercus suber) forests. In a previous transcriptome analysis, we reported on its immunity against Phytophthora cinnamomi. However, little is known about the involvement of secondary metabolites on P. purpurea defence response. It is known though that root exudates are toxic to this pathogen. To understand the involvement of secondary metabolites in the defence of P. purpurea, a metabolome analysis was performed using leaves and roots of plants challenged with the pathogen along 72 h. The compounds putatively identified in challenged plants were constitutively produced. Alkaloids, fatty acids, flavonoids, glucosinolates, polyketides, prenol lipids, phenylpropanoids, sterols and terpenoids, were differentially produced in leaves or roots along the experiment timescale. It must be emphasized the constitutive production of taurine in leaves and its increase soon after challenging which suggests its role in P. purpurea immunity to the stress imposed by the oomycete. The rapid increase of secondary metabolites production by this plant species accounts for a concerted action of multiple compounds and genes on innate protection of P. purpurea against P. cinnamomi. The combination of metabolome with the transcriptome data previously disclosed, confirms the mentioned auto-immunity of this plant to a devastating pathogen and suggests its potential as antagonist for phytopathogens biological control opening a way for its application in green forestry / agriculture.

opencc-zeroApr 2023View details →

Data for: Variation in density, immune gene suppression, and co-infection outcomes among strains of the aphid endosymbiont Regiella insecticola

Many insects harbor heritable microbes that influence host phenotypes. Symbiont strains establish at different densities within hosts. This variation is important evolutionarily because within-host density has been linked to the costs and benefits of the symbiosis for both partners. Studying the factors shaping within-host density is important to our broader understanding of host-microbe coevolution. Here we focused on different strains of Regiella insecticola, a facultative symbiont of aphids. We first showed that strains of Regiella establish in pea aphids at drastically different densities. We then found that variation in density is correlated with the expression levels of two key insect immune system genes (phenoloxidase and hemocytin), with the suppression of immune gene expression correlating with higher Regiella density. We then performed an experiment where we established co-infections of a higher- and a lower-density Regiella strain, and we showed that the higher-density strain is better able to persist in co-infections than the lower-density strain. Together, our results point to a potential mechanism that contributes to strain-level variation in symbiont density in this system, and our data suggest that symbiont fitness may be increased by establishing at higher density within hosts. Our work highlights the importance of within-host dynamics shaping symbiont evolution.

Safety and immunogenicity of heterologous booster immunization with Ad5-nCoV after three-dose priming with inactivated SARS-CoV-2 vaccine in Chinese adults: a randomized, double-blind, parallel-controlled trial

Data on safety and immunity of heterologous booster (fourth dose) after three-dose priming with inactivated SARS-CoV-2 vaccine are limited in Chinese adults. Here, we evaluate the safety and immunogenicity of immunization with Ad5-nCoV in a randomized, double-blind, parallel-controlled phase 4 clinical trial in Zhejiang, China (NCT05373030). Participants aged 18-80 years (100 participants per group) who have administered three doses of inactivated SARS-CoV-2 vaccine ≥ 6-month earlier were enrolled and randomized at 1:1 into two groups, then administered intramuscular Ad5-nCoV or different inactivated SARS-CoV-2 vaccine (CoronaVac or Covilo) respectively. All observed adverse reactions were predictable and manageable. Ad5-nCoV elicited significantly higher RBD-specific IgG levels, with a GMC of 2924.0 on day 14 post-booster, 7.8-fold that of the inactivated vaccine. Pseudovirus-neutralizing antibodies to Omicron BA.4/5 showed a similar pattern, with GMT of 228.9 in the Ad5-nCoV group and 65.5 in the inactivated vaccine group. The Ad5-nCoV booster-maintained a high antibody levels on day 90, with seroconversion of 71.4%, while the inactivated vaccine group was 5.2%, closed to pre-booster levels. In summary, a fourth Ad5-nCoV vaccination following three-dose inactivated SARS-CoV-2 vaccination is immunogenic, tolerable, and more efficient than inactivated SARS-CoV-2 vaccine. Ad5-nCoV elicits a stronger humoral response against Omicron BA.4/5 and maintains antibody levels for longer than homologous boosting.

Combined immune checkpoint blockade increases myocardial secretion of H-FABP, NT-Pro-BNP, NLRP-3 inflammasome, Interleukin-1β and Interleukin-6: biochemical implications in cardio-immuno-oncology

Background: Immune checkpoint inhibitors have transformed the treatment of several cancers by releasing restrained antitumor immune responses. Ipilimumab, an anti–cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) antibody, and nivolumab, an anti–programmed death-1 (PD-1) antibody, have individually improved survival in patients with melanoma, and their combination further enhances antitumor activity and survival. More recently, an anti-LAG3 human monoclonal antibody, Relatlimab, has been approved by FDA for combinatorial treatment with Nivolumab for metastatic melanoma and an anti-PD-L1 mAb,Atezolizumab, is undergoing clinical trials evaluation in combination with Ipilimumab for metastatic lung cancer.However,adverse events associated with these agents include dermatitis, endocrinopathies, colitis, hepatitis, and pneumonitis, which are all thought to arise from aberrant activation of autoreactive T cells. These toxic effects are more frequent and severe when immunomodulatory mAbs are used in combination.                       Methods: human cardiomyocytes co-cultured with hPBMC were exposed to monotherapy and combinatorial ICIs (PD-L1 and  CTLA-4 or PD-1 and  LAG-3 blocking agents, at 200 nM) for 48 h. After treatments, cardiac cell lysis and secretion of biomarkers of cardiotoxicity (H-FABP, NT-Pro-BNP), NLRP3-inflammasome and Interleukin 1 and 6 were determined through colorimetric and enzymatic assays.                                                                                                                                                    Results:Both Combinations of immune checkpoint inhibitors  exertmore potent cardiotoxic side effects compared to monotherapies against human cardiac cells co-cultured with human lymphocytes. LDH release from cardiac cells was 43% higher in PDL-1/CTLA-4 blocking agents, and 35.7% higher  in PD-1/LAG-3 blocking agents compared to monotherapies. Biomarkers of cardiotoxicity, such as  H-FABP and NT-Pro-BNP were also strongly increased in combination therapy than monotherapies. NLRP3 inflammasome, IL-1β and IL-6 levels were also increased by PDL-1/CTLA-4 and PD-1/LAG-3 combined blocking agents compared to untreated cells and monotherapies.                                                                    Conclusions:Data of the present study, although in vitro, indicate that combinatorial immune checkpoint blockade on co-cultures of hPBMCs and cardiac cells, including for the first time the anti LAG-3 monoclonal antibody, induce a pro- inflammatory phenotype, thus indicating that these therapies should be closely monitored by the multidisciplinary team consisting of oncologists, cardiologists and immunologists.

opencc-by-4.0Feb 2023View details →

Germline Immunomodulatory Expression Quantitative Trait Loci (ieQTLs) Associated with Immune-Related Toxicity from Checkpoint Inhibition

Robert Ferguson1,2,3*, Vylyny Chat1,2,3*, Leah Morales1,2,3, Danny Simpson1,2,3, Kelsey Monson1,2,3, Elisheva Cohen1,2,3,Sarah Zusin1,2,3, Gabriele Madonna4, Mariaelena Capone4, Ester Simeone4, Anna Pavlick5, Jason Luke6,7, Thomas F Gajewski8,9,10, Iman Osman1,3,11,12, Paolo Antonio Ascierto4, Jeffrey Weber1,3,11, Tomas Kirchhoff1,2,3 1Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, NY, USA 2Departments of Population Health and Environmental Medicine, New York University- Grossman School of Medicine, New York, NY, USA 3The Interdisciplinary Melanoma Cooperative Group, New York University-Grossman School of Medicine, New York, NY, USA 4Melanoma Cancer Immunotherapy and Innovative Therapy Unit, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Napoli, Italy 5Division of Hematology & Medical Oncology, the Cutaneous Oncology Program, Weill Cornell Medicine and New York-Presbyterian, New York, USA 6Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15213, USA. 7UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA. 8Department of Pathology, University of Chicago, Chicago, IL, USA. 9Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA. 10Ben May Department for Cancer Research, University of Chicago, Chicago, IL, USA. 11Department of Medicine, New York University-Grossman School of Medicine, New York, NY, USA 12Ronald O. Perelman Department of Dermatology, New York University-Grossman School of Medicine, New York, NY, USA *These authors contributed equally to the work Corresponding author: Tomas Kirchhoff, PhD ABSTRACT Background: Immune-checkpoint inhibition (ICI) has improved clinical outcomes for metastatic melanoma patients, however, 65-80% of patients treated with ICI experience immune-related adverse events (irAEs). Given the plausible link of irAEs with underlying host immunity, we explored if germline genetic variants controlling the expression of 42 immunomodulatory genes were associated with the risk of irAEs in melanoma patients treated with the single-agent anti- CTLA-4 antibody ipilimumab (IPI). Methods: We identified 42 immunomodulatory expression quantitative trait loci (ieQTLs) most significantly associated with the expression of 382 immune-related genes. These germline variants were genotyped in IPI-treated melanoma patients, collected as part of a multiinstitutional collaboration. We tested the association of ieQTLs with irAEs in a discovery cohort of 95 patients followed by validation in an additional 97 patients. Results: We found that the alternate allele of rs7036417, a variant linked to increased expression of SYK, was strongly associated with an increased risk of grade 3-4 toxicity (OR= 7.46; 95% CI=2.65-21.03; p=1.43E-04). This variant was not associated with response (OR= 0.90; 95% CI=0.37-2.21; p=0.82). Conclusion: We report that rs7036417 associates with increased risk of severe irAEs, independent of IPI efficacy. SYK plays an important role in B-cell/T-cell expansion and increased pSYK has been reported in patients with autoimmune disease. The association between rs7036417 and IPI irAEs in our data suggests a role of SYK over-expression in irAE development. These findings support the hypothesis that inherited variation in immune-related pathways modulate ICI toxicity and suggest SYK as a possible future target for therapies to reduce irAEs.   Keywords: irAEs; germline variants; immune checkpoint inhibition; melanoma Funding: This research was funded by the Italian Ministry of Health (IT-MOH) through “Ricerca Corrente”, grants number M2/2 and L2-1.

Interaction of Bacteria, Immune Cells, and Surface Topography in Periprosthetic Joint Infections

This record contains raw data related to article “Interaction of Bacteria, Immune Cells, and Surface Topography  in Periprosthetic Joint Infections”

opencc-by-4.0Mar 2023View details →

Benchmark datasets for "Detecting T-cell expansion and quantifying clone survival from deep profiling of immune repertoires"

T-cell receptor repertoire sequencing datasets describing time courses obtained for vaccination, normal aging and blood transplant cases. Datasets reported here were previously published (except for Tem/Tcm data), this is just a compendium of selected samples that is properly pre-processed and formatted.

opencc-by-4.0Dec 2022View details →

CD4 T cell receptor hierarchies are stable and independent of HIV-mediated dysregulation of immune homeostasis

LT-ART and A5248 folders contain preprocessed CyTOF files (FCS format) from a 31-marker mass cytometry panel to examine all major PBMC lineages and specifically CD4 and CD8 T cell memory dynamics in people with HIV (PWH) who are durably ART suppressed for an average of 6.7 years (LT-ART, n = 10) and PWH in the first 500 days following ART initiation (A5248, n = 10). The panel also includes markers of activation (HLA-DR, CD38, CCR5), activation/exhaustion (PD-1), proliferation (Ki67), survival (Bcl-2) and long-lived memory (CD127). Preprocessed annotated data objects (A5248_subsample.h5ad, LT-ART_subsample.h5ad) for unsupervised analysis can be accessed using the 'read_h5ad' function in Scanpy. CD4_MSI and CD8_MSI folders contain the MSI data for the Gamma fixed-effects regression models.  All source code for reproduction of the results can be found in the GitHub repository: <a href="https://github.com/glab-hiv/immune-recovery">https://github.com/glab-hiv/immune-recovery</a>

TSPO acts as an immune resistance gene involved in the T cell mediated immune control of glioblastoma

Glioblastoma (GB) IDH-wildtype is the most malignant primary brain tumor. It is particularly resistant to current immunotherapies. Translocator protein 18 kDa (TSPO) is upregulated in GB and correlates with malignancy and poor prognosis, but also with increased immune infiltration. Here, we studied the role of TSPO in the regulation of immune resistance of human GB cells. The role of TSPO in tumor immune resistance was experimentally determined in primary brain tumor initiating cells (BTICs) and cell lines through genetic manipulation of TSPO expression and subsequent cocultures with antigen specific cytotoxic T cells and autologous tumor-infiltrating T cells. Death inducing intrinsic and extrinsic apoptotic pathways affected by TSPO were investigated. TSPO-regulated genes mediating apoptosis resistance in BTICs were identified through gene expression analysis and subsequent functional analyses. TSPO transcription in primary GB cells correlated with CD8+ T cell infiltration, cytotoxic activity of T cell infiltrate, expression of TNFR and IFNGR and with the activity of their downstream signalling pathways, as well as with the expression of TRAIL receptors. Coculture of BTICs with tumor reactive cytotoxic T cells or with T cell-derived factors induced TSPO up-regulation through T cell derived TNFα and IFNγ. Silencing of TSPO sensitized BTICs against T cell-mediated cytotoxicity. TSPO selectively protected BTICs against TRAIL-induced apoptosis by regulating apoptosis pathways. TSPO also regulated the expression of multiple genes associated with resistance against apoptosis. We conclude that TSPO expression in GB is induced through T cell-derived cytokines TNFα and IFNγ and that TSPO expression protects GB cells against cytotoxic T cell attack through TRAIL. Our data thereby provide an indication that therapeutic targeting of TSPO may be a suitable approach to sensitize GB to immune cell-mediated cytotoxicity by circumventing tumor intrinsic TRAIL resistance.

openJun 2023View details →

IL-18 couples innate and adaptive immune cell activation in acute multisystem inflammatory syndrome in children (MIS-C)

This repository contains the scRNA-Seq data (including TCR-Seq and BCR-Seq data) set used in the manuscript titled "IL-18 couples innate and adaptive immune cell activation in acute multisystem inflammatory syndrome in children (MIS-C)". This dataset is generated from 10x cell ranger software. In the study, we have 10 PBMC samples, from 5 MIS-C children at paired time points. T1 stands for admission time and T3 follow-up time, about 1 month post hospital discharge.

opencc-by-4.0Jun 2023View details →

Immune single-cell RNA-seq data from PyMT-M tumor and its peripheral blood samples

Immune single-cell RNA-seq data collection and preprocessing Blood and tumor samples were harvested from PyMT-M tumor-bearing mice. Blood samples (n=3) are collected retro-orbitally using caliper tubes and processed with red blood cell lysis buffer (Tonbo Biosciences) before library preparation. A tumor sample are dissociated with Tumor Dissociation Kit following the manufacturer’s instructions (Miltenyi Biotec). After isolation and filtering through a 70µm filter, CD45+DAPI- cells were sorted using FACSAria cell sorter (BD Biosciences) at the Cytometry and Cell Sorting Core. The single-cell libraries were prepared using Chromium Controller (10X Genomics) at the Single Cell Genomics Core and sequenced using NovaSeq 6000 at the Genomics and RNA Profiling Core of Baylor College of Medicine. The FASTQ files were processed using Cell Ranger pipelines (10X Genomics) to generate feature-barcode matrices. Integrating immune single-cell RNA-seq data from the blood and tumor of PyMT-M mouse We followed the Seurat tutorial on single-cell RNA integration from <a href="https://satijalab.org/seurat/articles/integration_introduction.html">https://satijalab.org/seurat/articles/integration_introduction.html</a>. Specifically, both datasets were library-size normalized and log-scaled. Then, variable genes from both datasets were extracted, and overlapped variable genes were used as anchors to integrate the two datasets to generate a combined immune single-cell RNA-seq dataset.   Immune cell type annotation using SingleR After having the integrated immune single-cell RNA-sequencing data, we performed the standard pipeline for clustering, including scaling the expression data, performing dimension reduction using PCA and UMAP, and finding clusters by a shared nearest neighbor (SNN) modularity optimization (<a href="https://satijalab.org/seurat/articles/integration_introduction.html">https://satijalab.org/seurat/articles/integration_introduction.html</a>). Then, we used the R package SingleR to assign cell-type labels to each identified cluster using the ImmGen reference data from the Immunological Genome Project.

opencc-zeroJun 2023View details →

Data from: The CD73 immune checkpoint promotes tumor cell metabolic fitness

CD73 is an ectonucleotidase overexpressed on tumor cells that suppresses anti-tumor immunity. Accordingly, several CD73 inhibitors are currently being evaluated in the clinic, including in large randomized clinical trials. Yet, the tumor cell-intrinsic impact of CD73 remains largely uncharacterized. Using metabolomics, we discovered that CD73 significantly enhances tumor cell mitochondrial respiration and aspartate biosynthesis. Importantly, rescuing aspartate biosynthesis was sufficient to restore proliferation of CD73-deficient tumors in immune-deficient mice. Seahorse analysis of a large panel of mouse and human tumor cells demonstrated that CD73 enhanced oxidative phosphorylation (OXPHOS) and glycolytic reserve. Targeting CD73 decreased tumor cell metabolic fitness, increased genomic instability and suppressed poly ADP ribose polymerase (PARP) activity. Our study thus uncovered an important immune-independent function for CD73 in promoting tumor cell metabolism and provides the rationale for previously unforeseen combination therapies incorporating CD73 inhibition.

opencc-by-4.0Jul 2023View details →

Data : Effects of Fructooligosaccharides (FOS) on the Immune Response of the Shrimp Penaeus vannamei and on the Reduction in Vibrio spp. and Pseudomonas spp. in Cultures of Post-Larvae.

Data related with Corrales Barrios, Y.; Roncarati, A.; Martín Ríos, L.D.; Rodríguez González, M.; González Salotén, M.; López Zaldívar, Y.; Arenal, A. Effects of Fructooligosaccharides (FOS) on the Immune Response of the Shrimp Penaeus vannamei and on the Reduction in Vibrio spp. and Pseudomonas spp. in Cultures of Post-Larvae. Microbiol. Res. 2023, 14,

opencc-by-4.0Jul 2023View details →

A novel immune-related prognostic signature based on Chemoradiotherapy sensitivity predicts long-term survival in patients with esophageal squamous cell carcinoma.

Raw Data for PeerJ

opencc-by-4.0Mar 2023View details →

Interferon-inducible phospholipids govern IFITM3-dependent endosomal antiviral immunity

Raw data from indicated Figures of our work entitled "Interferon-inducible phospholipids govern IFITM3-dependent endosomal antiviral immunity" by Unali et al., published as Open Access in EMBO J.

opencc-zeroJul 2023View details →

Data from: Genetic variation at innate and adaptive immune genes - contrasting patterns of differentiation and local adaptation in a wild gull

Immunogenetic variation in natural vertebrate populations is expected to respond to spatial and temporal fluctuations in pathogen assemblages. While spatial heterogeneity in pathogen-driven selection enhances local immunogenetic adaptations and population divergence, different immune genes may yield contrasting responses to the environment. Here, we investigated population differentiation at the key pathogen recognition genes of the innate and adaptive immune system in a colonial bird species, the black headed gull Chroicocephalus ridibundus. We assessed genetic variation at three toll-like receptor (TLR) genes (innate immunity) and the major histocompatibility complex (MHC) class I and II genes (adaptive immunity) in gulls from seven colonies scattered across Poland. As expected, we found much greater polymorphism at the MHC than TLRs. Population differentiation at the MHC class II, but not MHC-I, was significantly stronger than at neutral microsatellite loci, suggesting local adaptation. This could reflect spatial variation in the composition of extra-cellular parasite communities (e.g. helminths), possibly driven by sharp differences in habitat structure between colonies. Despite contrasting patterns of population differentiation, both MHC classes showed similar regimes of diversifying selection. Some significant population differentiation was also observed at TLRs, suggesting that innate immune receptors may respond to fine-scale spatial variation in pathogen pressure, although this pattern could have been enhanced by drift. Our results suggested that local adaptation at the pathogen recognition immune genes can be maintained at relatively small or moderate spatial scales in species with high dispersal potential and highlighted the complexity of immunogenetic responses of animals to heterogeneous environments.

opencc-zeroAug 2023View details →

Transformable nano-antibiotics for mechanotherapy and immune activation against drug-resistant Gram-negative bacteria

The dearth of antibiotic candidates against Gram-negative bacteria and the rise of antibiotic resistance create a global health concern. The challenge lies in the unique Gram-negative bacterial outer membrane that provides the impermeable barrier for antibiotics and sequesters antigen presentation. We designed a transformable nano-antibiotics (TNA) which can transform from nontoxic nanoparticles to bactericidal nanofibrils with reasonable rigidity (Young's modulus, 21.6 ± 5.9 MPa) after targeting β-barrel assembly machine A (BamA) and lipid polysaccharides (LPS) of Gram-negative bacteria. After morphological transformation, the TNA can penetrate and damage the bacterial envelope, disrupt electron transport and multiple conserved biosynthetic and metabolic pathways, burst bacterial antigen release from the outer membrane, and subsequently activate innate and adaptive immunity. TNA kills Gram-negative bacteria in vitro and in vivo with undetectable resistance through multiple bactericidal modes of action. TNA-treatment-induced vaccination results in rapid and long-lasting immune responses, protecting against lethal re-infections.

opencc-zeroAug 2023View details →

Multimodal immune profiling of SARS-CoV-2 in Uganda – soluble immune mediators

Little is known about the pathobiology of SARS-CoV-2 infection in sub-Saharan Africa, where severe COVID-19 fatality rates are among the highest in the world and the immunological landscape is unique. In a prospective cohort study of 306 adults encompassing the entire clinical spectrum of SARS-CoV-2 infection in Uganda, we integrated profiling of the peripheral blood proteome and transcriptome to dissect the immunopathology of COVID-19 across multiple phases of the pandemic. Beyond the prognostic importance of myeloid cell-driven immune activation and lymphopenia, we show that multifaceted impairment of host protein synthesis and extensive redox imbalance define core biological signatures of severe COVID-19, with central roles for IL-7, IL-15, and lymphotoxin-α in COVID-19 respiratory failure. While prognostic signatures were generally consistent in SARS-CoV-2/HIV-coinfection, type I interferon responses uniquely scaled with COVID-19 severity in persons living with HIV. Throughout the pandemic, COVID-19 severity peaked during phases dominated by A.23/A.23.1 and Delta B.1.617.2/AY variants. Independent of clinical severity, Delta phase COVID-19 was distinguished by exaggerated pro-inflammatory myeloid cell and inflammasome activation, NK and CD8+ T-cell depletion, and impaired host protein synthesis. Combining these analyses with a contemporary Ugandan cohort of adults hospitalized with influenza and other severe respiratory infections, we found activation of epidermal and platelet-derived growth factor pathways to be distinct features of COVID-19, deepening translational understanding of mechanisms potentially underlying SARS-CoV-2-associated pulmonary fibrosis. Collectively, our findings provide biological rationale for use of broad and targeted immunotherapies for severe COVID-19 in sub-Saharan Africa, illustrate the relevance of local viral and host factors to SARS-CoV-2 immunopathology, and highlight underemphasized yet therapeutically exploitable immune pathways driving COVID-19 severity.

opencc-by-4.0Dec 2022View details →

High risk clear cell renal cell carcinoma microenvironments contain protumour immunophenotypes lacking specific immune checkpoints.

Final Seurat file (rds) produced from the immune cell analysis performed in "High risk clear cell renal cell carcinoma microenvironments contain protumour immunophenotypes lacking specific immune checkpoints."