The secreted peptide IRP functions as a DAMP in rice immunity

ABSTRACTSmall signaling peptides play important roles in various plant processes, but information regarding their involvement in plant immunity is limited. We previously identified a novel small secreted protein in rice, named immune response peptide (IRP) by the integrated multi-omics analyses. Here, we studied IRP functions in rice immunity. Rice plants overexpressing IRP enhanced resistance to the blast fungus. Application of the IRP peptide to rice suspension cells triggered the expression of IRP itself and defense gene PAL1. RNA-seq results revealed that 84% of genes upregulated by IRP peptide were also induced by chitin, including 13 OsWRKY transcription factors, indicating that IRP and chitin share the similar signaling pathway. Co-treatment with chitin and IRP elevated the expression level of PAL1 and OsWRKYs in an additive manner. When results of IRP and PAL1 expression and MAPK activation by IRP were compared with those by chitin, IRP had a stronger effect on MAPK activation rather than IRP and PAL1 expression. Collectively, our findings indicate that IRP functions as a damage-associated molecular pattern (DAMP) in rice immunity, regulating MAPKs and OsWRKYs to amplify chitin signaling, and provide new insights into how PAMPs and DAMPs cooperatively regulate rice immunity.

Download Full-text

Osmotic stress activated protein kinase 5 (SAPK5) positively regulates immune response and blast resistance in rice

10.21203/rs.3.rs-54599/v1 ◽

2020 ◽

Author(s):

Xiaobo Zhu ◽

Xiaoyu Long ◽

WeiWei Ma ◽

Hui Shi ◽

Hong Yi ◽

...

Keyword(s):

Immune Response ◽

Disease Resistance ◽

Protein Kinase ◽

Osmotic Stress ◽

Protein Kinases ◽

Kinase Activity ◽

Blast Resistance ◽

Plant Immunity ◽

Molecular Pattern

Abstract Background The sucrose non-fermenting 1 (SNF1) related protein kinase 2 (SnRK2) family proteins are plant-specific Ser/Thr protein kinases that are mainly involved in response to abiotic stress. However, their regulation roles on immune response and disease resistance in crops are largely unknown. Results In this study, we report the characterization of a rice SnRK2 family member, osmotic stress activated protein kinases 5 (SAPK5), on plant immune response. The SAPK5 protein is localized in cytoplasm and possesses kinase activity. The kinase activity of SAPK5 is promoted upon treatment with chitin, a conserved pathogen-associated molecular pattern (PAMP). Knockout of SAPK5 compromises rice immune response and resistance against the fungal pathogen Magnaporthe oryzae. Conclusions Our study demonstrates that SAPK5 positively regulates immune response and disease resistance in rice and provides new insights into the regulatory roles of SnRK2 proteins on plant immunity.

Download Full-text

Integration of tumor inflammation, cell proliferation, and traditional biomarkers improves prediction of immunotherapy resistance and response

Biomarker Research ◽

10.1186/s40364-021-00308-6 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Sarabjot Pabla ◽

R. J. Seager ◽

Erik Van Roey ◽

Shuang Gao ◽

Carrie Hoefer ◽

...

Keyword(s):

Immune Response ◽

Cell Proliferation ◽

Cell Activation ◽

Response Rate ◽

Checkpoint Inhibitors ◽

Host Immune Response ◽

Gene Signature ◽

B Cell Activation ◽

Rna Seq ◽

Multiple Tumor

Abstract Background Contemporary to the rapidly evolving landscape of cancer immunotherapy is the equally changing understanding of immune tumor microenvironments (TMEs) which is crucial to the success of these therapies. Their reliance on a robust host immune response necessitates clinical grade measurements of immune TMEs at diagnosis. In this study, we describe a stable tumor immunogenic profile describing immune TMEs in multiple tumor types with ability to predict clinical benefit from immune checkpoint inhibitors (ICIs). Methods A tumor immunogenic signature (TIGS) was derived from targeted RNA-sequencing (RNA-seq) and gene expression analysis of 1323 clinical solid tumor cases spanning 35 histologies using unsupervised analysis. TIGS correlation with ICI response and survival was assessed in a retrospective cohort of NSCLC, melanoma and RCC tumor blocks, alone and combined with TMB, PD-L1 IHC and cell proliferation biomarkers. Results Unsupervised clustering of RNA-seq profiles uncovered a 161 gene signature where T cell and B cell activation, IFNg, chemokine, cytokine and interleukin pathways are over-represented. Mean expression of these genes produced three distinct TIGS score categories: strong (n = 384/1323; 29.02%), moderate (n = 354/1323; 26.76%), and weak (n = 585/1323; 44.22%). Strong TIGS tumors presented an improved ICI response rate of 37% (30/81); with highest response rate advantage occurring in NSCLC (ORR = 36.6%; 16/44; p = 0.051). Similarly, overall survival for strong TIGS tumors trended upward (median = 25 months; p = 0.19). Integrating the TIGS score categories with neoplastic influence quantified via cell proliferation showed highly proliferative and strong TIGS tumors correlate with significantly higher ICI ORR than poorly proliferative and weak TIGS tumors [14.28%; p = 0.0006]. Importantly, we noted that strong TIGS and highly [median = not achieved; p = 0.025] or moderately [median = 16.2 months; p = 0.025] proliferative tumors had significantly better survival compared to weak TIGS, highly proliferative tumors [median = 7.03 months]. Importantly, TIGS discriminates subpopulations of potential ICI responders that were considered negative for response by TMB and PD-L1. Conclusions TIGS is a comprehensive and informative measurement of immune TME that effectively characterizes host immune response to ICIs in multiple tumors. The results indicate that when combined with PD-L1, TMB and cell proliferation, TIGS provides greater context of both immune and neoplastic influences on the TME for implementation into clinical practice.

Download Full-text

Integration of RNA‐seq and RNAi reveals the contribution of znuA gene to the pathogenicity of Pseudomonas plecoglossicida and to the immune response of Epinephelus coioides

Journal of Fish Diseases ◽

10.1111/jfd.13502 ◽

2021 ◽

Author(s):

Le He ◽

Luying Wang ◽

Lingmin Zhao ◽

Zhixia Zhuang ◽

Xiaoru Wang ◽

...

Keyword(s):

Immune Response ◽

Epinephelus Coioides ◽

Rna Seq ◽

Pseudomonas Plecoglossicida

Download Full-text

A Puccinia striiformis f. sp. tritici secreted protein activates plant immunity at the cell surface

Scientific Reports ◽

10.1038/s41598-017-01100-z ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 16

Author(s):

Bayantes Dagvadorj ◽

Ahmet Caglar Ozketen ◽

Ayse Andac ◽

Cian Duggan ◽

Tolga Osman Bozkurt ◽

...

Keyword(s):

Cell Surface ◽

Puccinia Striiformis ◽

Plant Immunity ◽

Secreted Protein

Download Full-text

RNA-seq of muscle from pigs divergent in feed efficiency and product quality identifies differences in immune response, growth, and macronutrient and connective tissue metabolism

BMC Genomics ◽

10.1186/s12864-018-5175-y ◽

2018 ◽

Vol 19 (1) ◽

Cited By ~ 17

Author(s):

Justyna Horodyska ◽

Klaus Wimmers ◽

Henry Reyer ◽

Nares Trakooljul ◽

Anne Maria Mullen ◽

...

Keyword(s):

Immune Response ◽

Connective Tissue ◽

Product Quality ◽

Feed Efficiency ◽

Rna Seq ◽

Tissue Metabolism ◽

Connective Tissue Metabolism

Download Full-text

RNA Sequencing (RNA-Seq) Based Transcriptome Analysis in Immune Response of Holstein Cattle to Killed Vaccine against Bovine Viral Diarrhea Virus Type I

Animals ◽

10.3390/ani10020344 ◽

2020 ◽

Vol 10 (2) ◽

pp. 344 ◽

Cited By ~ 3

Author(s):

Bryan Irvine Lopez ◽

Kier Gumangan Santiago ◽

Donghui Lee ◽

Seungmin Ha ◽

Kangseok Seo

Keyword(s):

Immune Response ◽

Enrichment Analysis ◽

Receptor Interaction ◽

Type I ◽

Rna Seq ◽

Diarrhea Virus ◽

Viral Diarrhea ◽

Kegg Pathways ◽

Viral Diarrhea Virus

Immune response of 107 vaccinated Holstein cattle was initially obtained prior to the ELISA test. Five cattle with high and low bovine viral diarrhea virus (BVDV) type I antibody were identified as the final experimental animals. Blood samples from these animals were then utilized to determine significant differentially expressed genes (DEGs) using the RNA-seq transcriptome analysis and enrichment analysis. Our analysis identified 261 DEGs in cattle identified as experimental animals. Functional enrichment analysis in gene ontology (GO) annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways revealed the DEGs potentially induced by the inactivated BVDV type I vaccine, and might be responsible for the host immune responses. Our findings suggested that inactivated vaccine induced upregulation of genes involved in different GO annotations, including antigen processing and presentation of peptide antigen (via MHC class I), immune response, and positive regulation of interferon-gamma production. The observed downregulation of other genes involved in immune response might be due to inhibition of toll-like receptors (TLRs) by the upregulation of the Bcl-3 gene. Meanwhile, the result of KEGG pathways revealed that the majority of DEGs were upregulated and enriched to different pathways, including cytokine-cytokine receptor interaction, platelet activation, extracellular matrix (ECM) receptor interaction, hematopoietic cell lineage, and ATP-binding cassette (ABC) transporters. These significant pathways supported our initial findings and are known to play a vital role in shaping adaptive immunity against BVDV type 1. In addition, type 1 diabetes mellitus pathways tended to be significantly enriched. Thus, further studies are needed to investigate the prevalence of type 1 diabetes mellitus in cattle vaccinated with inactivated and live BVDV vaccine.

Download Full-text

HOS15 is a transcriptional corepressor of NPR1-mediated gene activation of plant immunity

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2016049117 ◽

2020 ◽

Vol 117 (48) ◽

pp. 30805-30815

Author(s):

Mingzhe Shen ◽

Chae Jin Lim ◽

Junghoon Park ◽

Jeong Eun Kim ◽

Dongwon Baek ◽

...

Keyword(s):

Gene Expression ◽

Ubiquitin Ligase ◽

Transcriptional Activation ◽

Plant Immunity ◽

Gene Activation ◽

Transcriptional Corepressor ◽

Defense Gene Expression ◽

Dynamic Regulation ◽

Defense Gene ◽

Transcriptional Corepressors

Transcriptional regulation is a complex and pivotal process in living cells. HOS15 is a transcriptional corepressor. Although transcriptional repressors generally have been associated with inactive genes, increasing evidence indicates that, through poorly understood mechanisms, transcriptional corepressors also associate with actively transcribed genes. Here, we show that HOS15 is the substrate receptor for an SCF/CUL1 E3 ubiquitin ligase complex (SCFHOS15) that negatively regulates plant immunity by destabilizing transcriptional activation complexes containing NPR1 and associated transcriptional activators. In unchallenged conditions, HOS15 continuously eliminates NPR1 to prevent inappropriate defense gene expression. Upon defense activation, HOS15 preferentially associates with phosphorylated NPR1 to stimulate rapid degradation of transcriptionally active NPR1 and thus limit the extent of defense gene expression. Our findings indicate that HOS15-mediated ubiquitination and elimination of NPR1 produce effects contrary to those of CUL3-containing ubiquitin ligase that coactivate defense gene expression. Thus, HOS15 plays a key role in the dynamic regulation of pre- and postactivation host defense.

Download Full-text

Comparison of human and mouse tissues with focus on genes with no 1-to-1 homology

10.1101/2021.05.22.445250 ◽

2021 ◽

Author(s):

Jieun Jeong ◽

Manolis Kellis

Keyword(s):

Immune Response ◽

Target Genes ◽

Expression Patterns ◽

Adaptive Immune Response ◽

Mouse Skin ◽

Rna Seq ◽

Therapy Targets ◽

Mouse Tissues ◽

Tissues Expression ◽

Human And Mouse

We assembled a panel of 28 tissue pairs of human and mouse with RNA-Seq data on gene expression. We focused on genes with no 1-to-1 homology, because they pose special challenges. In this way, we identified expression patterns that identify and explain differences between the two species and suggest target genes for therapeutic applications. Here we mention three examples. One pattern is observed by defining the aggregate expression of immunoglobulin genes (which have no homology) as a measure of different levels of an immune response. In Lung, we used this statistic to find genes that have significantly higher expression in low/moderate response, and thus they may be therapy targets: increasing their expression or mimicking their function with medications may help in recovery from inflammation in the lungs. Some of the observed associations are common to human and mouse; other associations involve genes involved in cell-to-cell signaling or in regeneration but were not known to be important in Lung. Second pattern is that in the Small Intestine, mouse expresses much less antimicrobial defensins, while it has much higher expression of enzymes that are found to improve adaptive immune response. Such enzymes may be tested if they improve probiotic supplements that help in gut inflammation and other diseases. Another pattern involves a many-to-many homology group of defensins that did not have a described function. In human tissues, expression of its genes was found only in a study of a disease of hair covered skin, but several of its genes are highly expressed in two tissues of our panel: mouse Skin and to a lesser degree mouse Vagina. This suggests that those genes or their homologs in other species may provide non-antibiotic medications for hair covered skin and other tissues with microbiome that includes fungi.

Download Full-text

Predicting Experimental Sepsis Survival with a Mathematical Model of Acute Inflammation

Frontiers in Systems Biology ◽

10.3389/fsysb.2021.755913 ◽

2021 ◽

Vol 1 ◽

Author(s):

Jared Barber ◽

Amy Carpenter ◽

Allison Torsey ◽

Tyler Borgard ◽

Rami A. Namas ◽

...

Keyword(s):

Immune Response ◽

Growth Rate ◽

Inflammatory Response ◽

Inflammatory Responses ◽

Initial Conditions ◽

Mortality Data ◽

Experimental Sepsis ◽

Initial Inoculum ◽

Molecular Pattern ◽

Parameter Values

Sepsis is characterized by an overactive, dysregulated inflammatory response that drives organ dysfunction and often results in death. Mathematical modeling has emerged as an essential tool for understanding the underlying complex biological processes. A system of four ordinary differential equations (ODEs) was developed to simulate the dynamics of bacteria, the pro- and anti-inflammatory responses, and tissue damage (whose molecular correlate is damage-associated molecular pattern [DAMP] molecules and which integrates inputs from the other variables, feeds back to drive further inflammation, and serves as a proxy for whole-organism health status). The ODE model was calibrated to experimental data from E. coli infection in genetically identical rats and was validated with mortality data for these animals. The model demonstrated recovery, aseptic death, or septic death outcomes for a simulated infection while varying the initial inoculum, pathogen growth rate, strength of the local immune response, and activation of the pro-inflammatory response in the system. In general, more septic outcomes were encountered when the initial inoculum of bacteria was increased, the pathogen growth rate was increased, or the host immune response was decreased. The model demonstrated that small changes in parameter values, such as those governing the pathogen or the immune response, could explain the experimentally observed variability in mortality rates among septic rats. A local sensitivity analysis was conducted to understand the magnitude of such parameter effects on system dynamics. Despite successful predictions of mortality, simulated trajectories of bacteria, inflammatory responses, and damage were closely clustered during the initial stages of infection, suggesting that uncertainty in initial conditions could lead to difficulty in predicting outcomes of sepsis by using inflammation biomarker levels.

Download Full-text