scholarly journals Robust transcriptional indicators of plant immune cell death revealed by spatio-temporal transcriptome analyses

2021 ◽  
Author(s):  
Jose Salguero-Linares ◽  
Irene Serrano ◽  
Nerea Ruiz-Solani ◽  
Marta Salas-Gomez ◽  
Ujjal Jyoti Phukan ◽  
...  
Keyword(s):  
Cell Death ◽  
Pseudomonas Syringae ◽  
Immune Cell ◽  
Expression Profiles ◽  
Pathogen Recognition ◽  
Time Zone ◽  
Fluorescent Reporter ◽  
Aaa Atpase ◽  
Regulated Cell Death ◽  
Spatio Temporal

Recognition of a pathogen by the plant immune system often triggers a form of regulated cell death traditionally known as the hypersensitive response. This type of immune cell death occurs precisely at the site of pathogen recognition, and it is restricted to a few cells. Extensive research has shed light into how plant immune receptors are mechanistically activated. However, a central key question remains largely unresolved: how does cell death zonation take place and what are the mechanisms that underpin this phenomenon? As a consequence, bona fide transcriptional indicators of immune cell death are lacking, which prevents gaining a deeper insight of its mechanisms before cell death becomes macroscopic and precludes any early or live observation. We addressed this question using the paradigmatic Arabidopsis thaliana - Pseudomonas syringae pathosystem, by performing a spatio-temporally resolved gene expression analysis that compared infected cells that will undergo immune cell death upon pathogen recognition vs by-stander cells that will stay alive and activate immunity. Our data revealed unique and time-dependent differences in the repertoire of differentially expressed genes, expression profiles and biological processes derived from tissue undergoing immune cell death and that of its surroundings. Further, we generated a pipeline based on concatenated pairwise comparisons between time, zone and treatment that enabled us to define 13 robust transcriptional immune cell death markers. Among these genes, the promoter of an uncharacterized AAA-ATPase has been used to obtain a fluorescent reporter transgenic line, which displays a strong spatio-temporally resolved signal specifically in cells that will later undergo pathogen-triggered cell death. In sum, this valuable set of genes can be used to define those cells that are destined to die upon infection with immune cell death-triggering bacteria, opening new avenues for specific and/or high-throughput techniques to study immune cell death processes at a single-cell level.

scholarly journals Pectobacterium carotovorum Elicits Plant Cell Death with DspE/F but the P. carotovorum DspE Does Not Suppress Callose or Induce Expression of Plant Genes Early in Plant–Microbe Interactions

2011 ◽  
Vol 24 (7) ◽  
pp. 773-786 ◽  
Author(s):  
Hye-Sook Kim ◽  
Phanit Thammarat ◽  
Steven A. Lommel ◽  
Clifford S. Hogan ◽  
Amy O. Charkowski
Keyword(s):  
Gene Expression ◽  
Cell Death ◽  
Pseudomonas Syringae ◽  
Plant Cell ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Secretion System ◽  
Broad Host Range ◽  
Pectobacterium Carotovorum ◽  
Callose Deposition

The broad-host-range bacterial soft rot pathogen Pectobacterium carotovorum causes a DspE/F-dependent plant cell death on Nicotiana benthamiana within 24 h postinoculation (hpi) followed by leaf maceration within 48 hpi. P. carotovorum strains with mutations in type III secretion system (T3SS) regulatory and structural genes, including the dspE/F operon, did not cause hypersensitive response (HR)-like cell death and or leaf maceration. A strain with a mutation in the type II secretion system caused HR-like plant cell death but no maceration. P. carotovorum was unable to impede callose deposition in N. benthamiana leaves, suggesting that P. carotovorum does not suppress this basal immunity function. Within 24 hpi, there was callose deposition along leaf veins and examination showed that the pathogen cells were localized along the veins. To further examine HR-like plant cell death induced by P. carotovorum, gene expression profiles in N. benthamiana leaves inoculated with wild-type and mutant P. carotovorum and Pseudomonas syringae strains were compared. The N. benthamiana gene expression profile of leaves infiltrated with Pectobacterium carotovorum was similar to leaves infiltrated with a Pseudomonas syringae T3SS mutant. These data support a model where Pectobacterium carotovorum uses the T3SS to induce plant cell death in order to promote leaf maceration rather than to suppress plant immunity.

scholarly journals Developmental cell death programs license cytotoxic cells to eliminate histocompatible partners

2016 ◽  
Vol 113 (23) ◽  
pp. 6520-6525 ◽  
Author(s):  
Daniel M. Corey ◽  
Benyamin Rosental ◽  
Mark Kowarsky ◽  
Rahul Sinha ◽  
Katherine J. Ishizuka ◽  
...  
Keyword(s):  
Cell Death ◽  
Immune Cell ◽  
Botryllus Schlosseri ◽  
Cell Type ◽  
Developmental Defects ◽  
Cytotoxic Cells ◽  
Regulated Cell Death ◽  
Loss Of Tolerance ◽  
Developmental Cell Death ◽  
Morula Cell

In a primitive chordate model of natural chimerism, one chimeric partner is often eliminated in a process of allogeneic resorption. Here, we identify the cellular framework underlying loss of tolerance to one partner within a natural Botryllus schlosseri chimera. We show that the principal cell type mediating chimeric partner elimination is a cytotoxic morula cell (MC). Proinflammatory, developmental cell death programs render MCs cytotoxic and, in collaboration with activated phagocytes, eliminate chimeric partners during the “takeover” phase of blastogenic development. Among these genes, the proinflammatory cytokine IL-17 enhances cytotoxicity in allorecognition assays. Cellular transfer of FACS-purified MCs from allogeneic donors into recipients shows that the resorption response can be adoptively acquired. Transfer of 1 × 105 allogeneic MCs eliminated 33 of 78 (42%) recipient primary buds and 20 of 76 (20.5%) adult parental adult organisms (zooids) by 14 d whereas transfer of allogeneic cell populations lacking MCs had only minimal effects on recipient colonies. Furthermore, reactivity of transferred cells coincided with the onset of developmental-regulated cell death programs and disproportionately affected developing tissues within a chimera. Among chimeric partner “losers,” severe developmental defects were observed in asexually propagating tissues, reflecting a pathologic switch in gene expression in developmental programs. These studies provide evidence that elimination of one partner in a chimera is an immune cell-based rejection that operates within histocompatible pairs and that maximal allogeneic responses involve the coordination of both phagocytic programs and the “arming” of cytotoxic cells.

scholarly journals The Role of Ferroptosis-Related Gene in the Immune Activity and Prognosis of Sepsis

2022 ◽  
Author(s):  
Wei Dai ◽  
Yu Tian ◽  
Deqiang Luo ◽  
Qian Xie ◽  
Fen Liu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Immune Cell ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
Therapeutic Interventions ◽  
Calibration Plot ◽  
Pathway Enrichment Analysis ◽  
Regulated Cell Death

IntroductionSepsis is a leading cause of mortality in intensive care units worldwide. Ferroptosis, a form of regulated cell-death–related iron, has been proven to be altered during sepsis, including increased iron transport and uptake into cells and decreased iron export. A better understanding of the role of ferroptosis in sepsis should expedite the identification of biomarkers for prognostic evaluation and therapeutic interventions.Material and methodsWe used the mRNA expression profiles of sepsis patients from Gene Expression Omnibus (GEO) to analyze the expression level of ferroptosis-related genes and construct molecular subtypes.ResultsTwo distinct ferroptosis patterns were determined, and the overall survival of the two clusters was highly significantly different. Gene comparison analysis was performed on these two groups, and there were a total of 106 differentially expressed genes(DEGs). Pathway enrichment analysis of these genes showed that ferroptosis and immune-related pathways were enriched, suggesting that immune pathways might be critically involved in sepsis. To systematically predict the prognosis of sepsis, we constructed a nomogram model, the calibration plot nomogram showed excellent concordance for the 7-, 14-, and 28-days predicted and actual overall survival probabilities. Finally, the results of bioinformatics analysis were validated in animal and cell modelsConclusionsIn this study, we construct a ferroptosis-related nomogram that can be used for prognostic prediction in sepsis. In addition, we revealed the ferroptosis played a non-negligible role in immune cell infiltration and guiding more effective immunotherapy strategies.

scholarly journals An Immunogenic Cell Death-Related Classification Predicts Prognosis and Response to Immunotherapy in Head and Neck Squamous Cell Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Xinwen Wang ◽  
Shouwu Wu ◽  
Feng Liu ◽  
Dianshan Ke ◽  
Xinwu Wang ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Clinical Outcomes ◽  
Immune Cell ◽  
Adaptive Immune Response ◽  
Immunogenic Cell Death ◽  
Consensus Clustering ◽  
Immune Microenvironment ◽  
Regulated Cell Death ◽  
Tumor Immune Microenvironment

Immunogenic cell death (ICD) has been classified as a form of regulated cell death (RCD) that is sufficient to activate an adaptive immune response. Accumulating evidence has demonstrated the ability of ICD to reshape the tumor immune microenvironment through the emission of danger signals or DAMPs, which may contribute to the immunotherapy. Currently, identification of ICD-associated biomarkers that stratify patients according to their benefit from ICD immunotherapy would be of great advantage. Here, we identified two ICD-associated subtypes by consensus clustering. ICD-high subtype was associated with the favorable clinical outcomes, abundant immune cell infiltration, and high activity of immune response signaling. Besides, we established and validated an ICD-related prognostic model that predicted the survival of HNSCC and was associated with tumor immune microenvironment. In conclusion, we established a new classification system of HNSCC based on ICD signatures. This stratification had significant clinical outcomes for estimating prognosis, as well as the immunotherapy of HNSCC patients

New Trends in Anti-Cancer Therapy: Combining Conventional Chemotherapeutics with Novel Immunomodulators

2018 ◽  
Vol 25 (36) ◽  
pp. 4758-4784 ◽  
Author(s):  
Amy L. Wilson ◽  
Magdalena Plebanski ◽  
Andrew N. Stephens
Keyword(s):  
Clinical Trials ◽  
Cell Death ◽  
Immune System ◽  
Cancer Therapy ◽  
Immune Cell ◽  
Cytotoxic T Lymphocyte ◽  
Tumour Microenvironment ◽  
Immune Checkpoints ◽  
Tumour Regression ◽  
Cell Trafficking

Cancer is one of the leading causes of death worldwide, and current research has focused on the discovery of novel approaches to effectively treat this disease. Recently, a considerable number of clinical trials have demonstrated the success of immunomodulatory therapies for the treatment of cancer. Monoclonal antibodies can target components of the immune system to either i) agonise co-stimulatory molecules, such as CD137, OX40 and CD40; or ii) inhibit immune checkpoints, such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death-1 (PD-1) and its corresponding ligand PD-L1. Although tumour regression is the outcome for some patients following immunotherapy, many patients still do not respond. Furthermore, chemotherapy has been the standard of care for most cancers, but the immunomodulatory capacity of these drugs has only recently been uncovered. The ability of chemotherapy to modulate the immune system through a variety of mechanisms, including immunogenic cell death (ICD), increased antigen presentation and depletion of regulatory immune cells, highlights the potential for synergism between conventional chemotherapy and novel immunotherapy. In addition, recent pre-clinical trials indicate dipeptidyl peptidase (DPP) enzyme inhibition, an enzyme that can regulate immune cell trafficking to the tumour microenvironment, as a novel cancer therapy. The present review focuses on the current immunological approaches for the treatment of cancer, and summarizes clinical trials in the field of immunotherapy as a single treatment and in combination with chemotherapy.

scholarly journals Cryo-EM structural analysis of FADD:Caspase-8 complexes defines the catalytic dimer architecture for co-ordinated control of cell fate

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Joanna L. Fox ◽  
Michelle A. Hughes ◽  
Xin Meng ◽  
Nikola A. Sarnowska ◽  
Ian R. Powley ◽  
...  
Keyword(s):  
Cell Death ◽  
Structural Analysis ◽  
Cell Fate ◽  
Catalytic Domain ◽  
Caspase 8 ◽  
Type I ◽  
Signaling Complex ◽  
Catalytic Domains ◽  
Regulated Cell Death ◽  
Death Effector

AbstractRegulated cell death is essential in development and cellular homeostasis. Multi-protein platforms, including the Death-Inducing Signaling Complex (DISC), co-ordinate cell fate via a core FADD:Caspase-8 complex and its regulatory partners, such as the cell death inhibitor c-FLIP. Here, using electron microscopy, we visualize full-length procaspase-8 in complex with FADD. Our structural analysis now reveals how the FADD-nucleated tandem death effector domain (tDED) helical filament is required to orientate the procaspase-8 catalytic domains, enabling their activation via anti-parallel dimerization. Strikingly, recruitment of c-FLIPS into this complex inhibits Caspase-8 activity by altering tDED triple helix architecture, resulting in steric hindrance of the canonical tDED Type I binding site. This prevents both Caspase-8 catalytic domain assembly and tDED helical filament elongation. Our findings reveal how the plasticity, composition and architecture of the core FADD:Caspase-8 complex critically defines life/death decisions not only via the DISC, but across multiple key signaling platforms including TNF complex II, the ripoptosome, and RIPK1/RIPK3 necrosome.

scholarly journals Uncoupling Salicylic Acid-Dependent Cell Death and Defense-Related Responses From Disease Resistance in the Arabidopsis Mutant acd5

Genetics ◽  
2000 ◽  
Vol 156 (1) ◽  
pp. 341-350
Author(s):  
Jean T Greenberg ◽  
F Paul Silverman ◽  
Hua Liang
Keyword(s):  
Cell Death ◽  
Salicylic Acid ◽  
Disease Resistance ◽  
Pseudomonas Syringae ◽  
Higher Plants ◽  
Ethylene Signaling ◽  
Symptom Development ◽  
Wild Type ◽  
Dependent Cell ◽  
Arabidopsis Mutant

Abstract Salicylic acid (SA) is required for resistance to many diseases in higher plants. SA-dependent cell death and defense-related responses have been correlated with disease resistance. The accelerated cell death 5 mutant of Arabidopsis provides additional genetic evidence that SA regulates cell death and defense-related responses. However, in acd5, these events are uncoupled from disease resistance. acd5 plants are more susceptible to Pseudomonas syringae early in development and show spontaneous SA accumulation, cell death, and defense-related markers later in development. In acd5 plants, cell death and defense-related responses are SA dependent but they do not confer disease resistance. Double mutants with acd5 and nonexpressor of PR1, in which SA signaling is partially blocked, show greatly attenuated cell death, indicating a role for NPR1 in controlling cell death. The hormone ethylene potentiates the effects of SA and is important for disease symptom development in Arabidopsis. Double mutants of acd5 and ethylene insensitive 2, in which ethylene signaling is blocked, show decreased cell death, supporting a role for ethylene in cell death control. We propose that acd5 plants mimic P. syringae-infected wild-type plants and that both SA and ethylene are normally involved in regulating cell death during some susceptible pathogen infections.

scholarly journals MBRS-19. SYNERGISM OF HDAC AND PARP INHIBITORS IN MYC-DRIVEN GROUP 3 MEDULLOBLASTOMA CELLS

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii401-iii401
Author(s):  
Johanna Vollmer ◽  
Jonas Ecker ◽  
Thomas Hielscher ◽  
Gintvile Valinciute ◽  
Sina Oppermann ◽  
...  
Keyword(s):  
Cell Death ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Parp Inhibitors ◽  
Class I ◽  
Trypan Blue Exclusion ◽  
Histone Deacetylase Inhibition ◽  
Cycle Arrest ◽  
Damage Repair ◽  
Group 3

Abstract Patients with MYC-driven Group 3 medulloblastoma (MB) show particularly poor outcome. It was previously shown that MYC-driven MBs are highly sensitive to class I histone deacetylase inhibition (HDACi). We studied the molecular effects of the class I HDACi entinostat in MYC-driven MB cells to identify potentially synergistic drug combinations, prioritizing drug clinical availability to enable clinical translation. Gene expression profiles of the MYC-amplified group 3 MB cell line HD-MB03 treated with entinostat were analyzed using bioinformatic approaches, identifying 29 altered biomechanisms. Overlay with a translational drug library of n=76 compounds resulted in 44 compounds targeting 9 biomechanisms. Filtering for publications supporting each drug′s role in MYC-driven entities, or functional interaction with HDACs, without publication of this combination in MBs, resulted in 5 compounds (olaparib, idasanutlin, ribociclib, selinexor, vinblastine). Synergism testing identified olaparib as the drug with the strongest synergism. Validation of the combination olaparib and entinostat by p.H2AX and PI staining as well as trypan blue exclusion showed increased double strand breaks (DSBs), increased cell death, loss of viability and cell numbers. Selectivity of MYC-amplified MB cells was shown by comparison to MYC-non amplified cell lines, which showed higher IC50s, and reacted with cell cycle arrest as opposed to cell death to the combination treatment. The role of HDACis in DNA damage repair was confirmed by increased DSBs when entinostat was added to the combination of olaparib with doxorubicin. Our study identified olaparib as a potential combination partner with entinostat for the treatment of MYC-driven Group 3 MB.

Lytic regulated cell death in aquaculture fish

2021 ◽  
Author(s):  
Xiaojing Xia ◽  
Bin He ◽  
Xiulin Zhang ◽  
Zhe Cheng ◽  
Mingcheng Liu ◽  
...  
Keyword(s):  
Cell Death ◽  
Regulated Cell Death ◽  
Aquaculture Fish
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