Characteristions of CRKP pneumonia at the single cell level
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE263380 | GEO | 2025/07/03
REPOSITORIES: GEO
Similar Datasets
Project description:Background and Aims: Unresolved hepatitis B virus (HBV) infection leads to a progressive state of immune exhaustion that impairs resolution of infection, leading to chronic infection (CHB). The immune-competent AAV-HBV mouse is a common HBV preclinical immune competent model, though a comprehensive characterization of the liver immune microenvironment and its translatability to human infection is still lacking. We investigated the intrahepatic immune profile of the AAV-HBV mouse model at a single-cell level and compared with data from CHB patients in immune tolerant (IT) and immune active (IA) clinical stages. Methods: Immune exhaustion was profiled through an iterative subclustering approach for cell-typing analyses of single-cell RNA-sequencing data in CHB donors and compared to the AAV-HBV mouse model 24-weeks post-transduction to assess its translatability. This was validated using an exhaustion flow cytometry panel at 40 weeks post-transduction. Results: Using single-cell RNA-sequencing, CD8 pre-exhausted T-cells with self-renewing capacity (TCF7+), and terminally exhausted CD8 T-cells (TCF7-) were detected in the AAV-HBV model. These terminally exhausted CD8 T-cells (expressing Pdcd1, Tox, Lag3, Tigit) were significantly enriched versus control mice and independently identified through flow cytometry. Importantly, comparison to CHB human data showed a similar exhausted CD8 T-cell population in IT and IA donors, but not in uninfected individuals. Conclusions: Long term high titer AAV-HBV mouse liver transduction led to T-cell exhaustion, as evidenced by expression of classical immune checkpoint markers at mRNA and protein levels. In both IT and IA donors, a similar CD8 exhausted T-cell population was identified, with increased frequency observed in IA donors. These data support the use of the AAV-HBV mouse model to study T-cell exhaustion in HBV infection and the effect of immune-based therapeutic interventions.
2024-12-31 | GSE244487 | GEO
Project description:To understand how the combination of ORIN1001 plus docetaxel promotes anti-tumor immunity, we performed single-cell RNA sequencing (scRNA-seq) of CD45+ cells from 2153L tumors. Our data found that combo induces CD8+ T cells that express high levels of T cell activation, cytotoxicity, and exhaustion genes. combo also increase the cDC1 and MHC-II high macrophages which exhibited higher M1-like macrophages scores.
2024-10-16 | GSE276356 | GEO
Project description:Acute myeloid leukemia (AML) relapse is associated with a poor prognosis. Natural killer (NK) cells therapy induce leukemia remission; however, NK cells were susceptible to be exhausted post infusion. Determination of the mechanism of NK cell exhaustion in AML patients may provide insights for enhancing AML therapy. Here, we investigated NK cell exhaustion in relapsed AML patients post allo-HSCT based on phenotypic, functional, and RNA sequencing analyses. Compared with those from the complete remission and healthy control groups, NK cells from the relapsed group exhibited less maturity, higher inhibitory receptor expression and poorer cytotoxicity. AML cells could induce NK cell exhaustion through inhibition of PI3K-AKT pathway. Activation of PI3K-AKT was effective to increase NK cell cytotoxicity in exhausted NK cells. Excessive activation of the NKG2A/HLA-E axis is responsible for the inhibition of the PI3K-AKT pathway. Anti-HLA-E restored NK cell cytotoxicity against AML by increasing the phosphorylation of AKT in exhausted NK cells and knockout of the klrc1 in NK92 cells increased the phosphorylation of AKT and cytotoxicity against THP-1 cells. Moreover, blocking NKG2A was effective in controlling NK cell exhaustion and promoting cytotoxicity in AML mice. In summary, AML cells induced NK cell exhaustion via excessive activation of NKG2A/HLA-E axis and inhibition on PI3K-AKT pathway. Blocking the NKG2A axis is an effective way to reverse the inhibition of PI3K-AKT signaling on exhausted NK cells.
2025-01-31 | GSE252702 | GEO
Project description:There is emerging interest in using proteomic data for environmental health-risk assessments. Meanwhile, due to attractive physicochemical properties, production and use of engineered nanomaterials (ENMs) are expanding with potential for exposure, thus necessitating toxicity information on these materials for human health risk analysis, where proteomic data can be informative. Here, cells (A549 human lung epithelial, J774 mouse monocyte/macrophage) were exposed to ENMs (nanoforms of SiO2, TiO2) of different sizes, surface chemistries (dose:0-100 ug/cm2, 24 h) for in vitro toxicity data. Cellular cytotoxicity (CTB, ATP, LDH), oxidative stress and proteomic analysis (MS-, antibody-based) were conducted post-nanoparticle (NP) exposures to determine cytotoxic potencies and identify molecular-level effects. Dose-, nanoform-, cell type-specific cytotoxicity changes were seen with both nanoSiO2 and nanoTiO2 exposures. Size, agglomeration, surface groups and metal impurities appeared to be cytotoxicity determinants. Proteomic data identified some common enriched mechanistic pathways relevant to phagocytosis, cell-shape changes, apoptosis, and inflammatory processes for nanoSiO2, nanoTiO2 exposed J774 cells. A549 cells exhibited pathway changes relevant to cell metabolism, endocytosis and inflammatory processes post-NP exposures. Concordance was seen between, cytotoxicity responses, notably cellular ATP, critical for cell viability, cellular oxidative stress and affected cellular pathways. These findings demonstrate the utility of proteomics in toxicology, warranting further exploration.
2024-08-12 | MSV000095579 | MassIVE
Project description:Engineered T cells transiently expressing tumor-targeting receptors are an attractive form of engineered T cell therapy as they carry no risk of insertional mutagenesis or long-term adverse side-effects. However, multiple rounds of treatment are often required, increasing patient discomfort and cost. To mitigate this, we sought to improve the antitumor activity of transient engineered T cells by screening a panel of small molecules targeting epigenetic regulators for their effect on T cell cytotoxicity. Using a model for engineered T cells targetting hepatocellular carcinoma, we find that short-term inhibition of G9a/GLP increases T cell antitumor activity in in vitro models and an orthotopic mouse model. G9a/GLP inhibition increases granzyme expression without terminal T cell differentiation or exhaustion and results in specific changes in expression of genes and proteins involved in pro-inflammatory pathways, T cell activation and cytotoxicity.
2023-01-19 | PXD039542 | JPOST Repository
Project description:This study investigates the downstream signaling pathways of T cell exhaustion by analyzing the changes in phosphotyrosine (pTyr) protein complexes using an integrated ion-exchange chromatography tandem mass tag (IEC-TMT) workflow. Peripheral blood mononuclear cells (PBMCs) from healthy donors were activated and co-cultured with tumor cells to induce T cell exhaustion. A trifunctional probe was developed to enrich pTyr protein complexes from the PBMC lysates. The captured complexes were then fractionated using IEC and analyzed by TMT-based quantitative proteomics. This approach allowed for the identification and quantification of 28 protein complexes. Differential analysis revealed significant changes in the abundance of several complexes, including the upregulation of lysosome-related complexes and downregulation of ER-related complexes, suggesting their potential roles in T cell exhaustion. Further investigation revealed that RTN4, a component of an upregulated lysosome-related complex, contributes to T cell exhaustion. Knockdown of RTN4 reversed T cell exhaustion and enhanced anti-tumor immunity, highlighting RTN4 as a potential therapeutic target.
2024-12-02 | PXD058458 |
Project description:High and moderate intensity endurance exercise alters gene expression in human white blood cells (WBCs), but the understanding of how this effect occurs is limited. To increase our knowledge of the nature of this process, we investigated the effects of passing the anaerobic threshold (AnT) on the gene expression profile in WBCs of athletes. Nineteen highly trained skiers participated in a treadmill test with an incremental step protocol until exhaustion (ramp test to exhaustion; RTE). The average total time to exhaustion was 14:40 min and time after AnT was 4:50 min. Two weeks later, seven of these skiers participated in a moderate treadmill test (MT) at 80% peak O2 uptake for 30 min, which was slightly below their AnTs. Blood samples were obtained before and immediately after both tests. RTE was associated with substantially greater leukocytosis and acidosis than MT. Gene expression in WBCs was measured using whole genome microarray expression analysis before and immediately after each test. A total of 310 upregulated genes were found after RTE, and 69 genes after MT, of which 64 were identical to RTE. Both tests influenced a variety of known gene pathways related to inflammation, stress response, signal transduction and apoptosis. A large group of differentially expressed, and previously unknown, small nucleolar RNA and small Cajal body RNA was found. In conclusion, a 15 min test to exhaustion was associated with substantially greater changes of gene expression than a 30 min test just below the AnT. After a general medical checkup, the subjects performed a ramp-type progressive exercise test on a treadmill. Blood samples were taken from the antecubital vein using indwelling catheter before (T0) and immediately after ramp test to exaustion (T1), and before (T2) and immediately after moderate treadmill test (T3).
2011-04-09 | E-GEOD-28498 | biostudies-arrayexpress
Project description:We investigated the effects of HIV infection on immune cell exhaustion at the transcriptomic level by analyzing single-cell RNA sequencing of peripheral blood mononuclear cells from four healthy subjects (37,847 cells) and six HIV-infected donors (28,610 cells). We identified nine immune cell clusters and eight T cell subclusters according to their unique gene expression programs; three of these (exhausted CD4+ and CD8+ T cells and interferon-responsive CD8+ T cells) were detected only in samples from HIV-infected donors. An inhibitory receptor KLRG1 was identified in the exhausted T cell populations and further characterized in HIV infected individuals. We identified a HIV-1 specific exhausted CD8+ T cell population expressing KLRG1, TIGIT, and T-betdimEomeshi markers. Ex-vivo antibody blockade of KLRG1 restored the function of HIV-specific exhausted CD8+ T cells demonstrating the contribution of KLRG1+ population to T cell exhaustion and providing an immunotherapy target to treat HIV chronic infection. Analysis of gene signatures also revealed impairment of B cell and NK cell function in HIV-infected donors. These data provide a comprehensive analysis of gene signatures associated with immune cell exhaustion during HIV infection, which could be useful in understanding exhaustion mechanisms and developing new cure therapies.
2020-09-12 | GSE157829 | GEO
Project description:Relatlimab (rela; anti-LAG-3) plus nivolumab (nivo; anti-PD-1) is safe and effective for treatment of advanced melanoma. We designed a trial (NCT03743766) where advanced melanoma patients received rela, nivo, or rela+nivo to interrogate the immunologic mechanisms of rela+nivo. Analysis of biospecimens from this ongoing trial demonstrated that rela+nivo led to enhanced capacity for CD8+ T cell receptor signaling and altered CD8+ T cell differentiation, leading to heightened cytotoxicity despite the retention of an exhaustion profile. Co-expression of cytotoxic and exhaustion signatures was driven by PRDM1, BATF, ETV7, and TOX. Effector function was upregulated in clonally expanded CD8+ T cells that emerged after rela+nivo. A rela+nivo intratumoral CD8+ T cell signature was associated with a favorable prognosis. This intratumoral rela+nivo signature was validated in peripheral blood as an elevated frequency of CD38+TIM3+CD8+ T cells. Overall, we demonstrated that cytotoxicity can be enhanced despite the retention of exhaustion signatures, which will inform future therapeutic strategies.
2024-08-11 | GSE225063 | GEO
Project description:Pediatric sepsis is a leading cause of mortality in children across the world. Within pediatric sepsis, how developmental age-specific host immune response impact on the occurrence and development of pediatric sepsis is still unknown, especially between infants and toddlers, which were the major susceptible age groups in sepsis. Experimental design In this study, we applied a nested case-control study strategy and analyzed the plasma proteomes of pediatric sepsis patients between infants and toddlers in comparison to their age-matched controls respectively. Each age group consists of three subgroups with different outcomes. One hundred and ten plasma samples were pooled into 16 samples for quantitative identification by LC-MS/MS. Results It was totally quantified 677 proteins. In comparison to toddlers, infant sepsis patients were characteristic with dominant neutrophil-mediated defense, suppressed adaptive immunity and NK-mediated cytotoxicity. Besides, pentose phosphate pathway was more up-regulated in infants and associated with poor outcome. Moreover, combined Hp and Thbs1 with the AUC value of 0.958 (95%CI, 0.868, 1.000) was confirmed as potential infant-adapted prognostic marker of poor outcome in sepsis. Conclusion and clinical relevance Our proteomic analysis of age-associated pediatric sepsis combined with clinical laboratory data provided a comprehensive insight into the complex, multifactorial heterogeneous host response to pediatric sepsis and allowed identification of critical differences between infant and toddler sepsis. Moreover, we confirmed that combined Hp and Thbs1 is more infant-adapted and serves as a potential prognostic biomarker for poor outcome of infant sepsis, promoting the application of age-adapted precision medicine in pediatric sepsis.
2021-11-01 | PXD026656 | Pride