scholarly journals Clustering Analysis of Splenocyte MicroRNAs in Pig Reveals the Key Signal Regulators in Immune Modulation of the Host During the Acute and Chronic Toxoplasma Gondii Infection

2021 ◽  
Author(s):  
Zhaofeng Hou ◽  
Hui Zhang ◽  
Kangzhi Xu ◽  
Shifan Zhu ◽  
Lele Wang ◽  
...  
Keyword(s):  
Immune Response ◽  
Toxoplasma Gondii ◽  
Immune Responses ◽  
Signaling Pathway ◽  
Hierarchical Clustering ◽  
Immune Regulation ◽  
Clustering Analysis ◽  
Expression Patterns ◽  
Signaling Molecules ◽  
Receptor Interaction

Abstract Background: Toxoplasma gondii is an obligatory intracellular protozoan parasite that can cause a geographically widespread zoonosis. Our previous splenocyte microRNA profiles analyses of pig infected with T. gondii revealed that the coordination of a large number of miRNAs regulates the host immune response during infection. However, the functions of more miRNAs involved to the immune regulation during T. gondii infection are not yet known.Methods: Clustering analysis was performed by K-means, self-organizing map (SOM) and Hierarchical clustering, respectively, to obtain miRNA groups with the similar expression patterns. Then, the target genes of miRNA group in each subcluster were further analyzed for function enrichment by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome pathway to recognize the key signaling molecules and the regulatory signatures of the innate and adaptive immune responses of the host during T. gondii infection.Results: A total of 252 miRNAs were successfully divided into 22 subclusters by K-means clustering (named by K1~K22), 29 subclusters by SOM clustering (named by SOM1~SOM29) and 6 subclusters by Hierarchical clustering (named by H1~H6) based on their dynamic expression levels in the different infection stages. A total of 634, 660 and 477 GO terms, 15, 26 and 14 KEGG pathways, and 16, 15 and 7 Reactome pathways were significantly enriched by K-means, SOM and Hierarchical clustering, respectively. Of note, up to 22 miRNAs mainly showing the downregulated expression at 50 DPI were identified into one subcluster (namely subcluster H3-K17-SOM1) through the three algorithms. Functional analysis revealed that a large group of immunomodulatory signaling molecules were controlled by the different miRNA groups to regulate multiple immune processes, for instance, IL-1-mediated cellular response and Th1/Th2 cell differentiation partly depending on Notch signaling transduction for subclusters K1 and K2, innate immune response involving to Neutrophil degranulation and TLR4 cascade signaling for subcluster K15, B cell activation for subclusters SOM17, SOM1 and SOM25, leukocyte migration and chemokine activity for subcluster SOM9, Cytokine-cytokine receptor interaction for subcluster H2, and interleukin production, chemotaxis of immune cells, Chemokine signaling pathway and C-type lectin receptor signaling pathway for subcluster H3-K17-SOM1.Conclusions: Clustering analysis of splenocyte microRNAs in pig reflected the key regulatory properties of subcluster miRNA molecules, as well as the important features in the immune regulation induced by acute and chronic infections of T. gondii. These results contribute to new insight into the identification of physiologic immune responses and maintenance of tolerance in pig spleen tissues during T. gondii infection.

scholarly journals Pattern of inflammatory immune response determines the clinical course and outcome of COVID-19: unbiased clustering analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Eunyoung Emily Lee ◽  
Kyoung-Ho Song ◽  
Woochang Hwang ◽  
Sin Young Ham ◽  
Hyeonju Jeong ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Clustering Analysis ◽  
Validation Cohort ◽  
Inflammatory Responses ◽  
Clinical Course ◽  
Severe Disease ◽  
Outcome Data ◽  
Inflammatory Immune Response ◽  
Cluster 2

AbstractThe objective of the study was to identify distinct patterns in inflammatory immune responses of COVID-19 patients and to investigate their association with clinical course and outcome. Data from hospitalized COVID-19 patients were retrieved from electronic medical record. Supervised k-means clustering of serial C-reactive protein levels (CRP), absolute neutrophil counts (ANC), and absolute lymphocyte counts (ALC) was used to assign immune responses to one of three groups. Then, relationships between patterns of inflammatory responses and clinical course and outcome of COVID-19 were assessed in a discovery and validation cohort. Unbiased clustering analysis grouped 105 patients of a discovery cohort into three distinct clusters. Cluster 1 (hyper-inflammatory immune response) was characterized by high CRP levels, high ANC, and low ALC, whereas Cluster 3 (hypo-inflammatory immune response) was associated with low CRP levels and normal ANC and ALC. Cluster 2 showed an intermediate pattern. All patients in Cluster 1 required oxygen support whilst 61% patients in Cluster 2 and no patient in Cluster 3 required supplementary oxygen. Two (13.3%) patients in Cluster 1 died, whereas no patient in Clusters 2 and 3 died. The results were confirmed in an independent validation cohort of 116 patients. We identified three different patterns of inflammatory immune response to COVID-19. Hyper-inflammatory immune responses with elevated CRP, neutrophilia, and lymphopenia are associated with a severe disease and a worse outcome. Therefore, targeting the hyper-inflammatory response might improve the clinical outcome of COVID-19.

scholarly journals Analysis of Structures and Epitopes of Surface Antigen Glycoproteins Expressed in Bradyzoites ofToxoplasma gondii

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Hua Cong ◽  
Min Zhang ◽  
Qingli Zhang ◽  
Jing Gong ◽  
Haizi Cong ◽  
...  
Keyword(s):  
Immune Response ◽  
Toxoplasma Gondii ◽  
Immune Responses ◽  
Surface Antigen ◽  
Protein Sequence ◽  
Protozoan Parasite ◽  
3D Models ◽  
Chronic Infections ◽  
Homologous Proteins ◽  
Protein Sequence Alignment

Toxoplasma gondiiis a protozoan parasite capable of infecting humans and animals. Surface antigen glycoproteins, SAG2C, -2D, -2X, and -2Y, are expressed on the surface of bradyzoites. These antigens have been shown to protect bradyzoites against immune responses during chronic infections. We studied structures of SAG2C, -2D, -2X, and -2Y proteins using bioinformatics methods. The protein sequence alignment was performed by T-Coffee method. Secondary structural and functional domains were predicted using software PSIPRED v3.0 and SMART software, and 3D models of proteins were constructed and compared using the I-TASSER server, VMD, and SWISS-spdbv. Our results showed that SAG2C, -2D, -2X, and -2Y are highly homologous proteins. They share the same conserved peptides and HLA-I restricted epitopes. The similarity in structure and domains indicated putative common functions that might stimulate similar immune response in hosts. The conserved peptides and HLA-restricted epitopes could provide important insights on vaccine study and the diagnosis of this disease.

scholarly journals Characterization of Embryonic Skin Transcriptome in Anser cygnoides at Three Feather Follicles Developmental Stages

2019 ◽  
Vol 10 (2) ◽  
pp. 443-454
Author(s):  
Chang Liu ◽  
Cornelius Tlotliso Sello ◽  
Yujian Sui ◽  
Jingtao Hu ◽  
Shaokang Chen ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Developmental Stages ◽  
De Novo ◽  
Transcriptome Assembly ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Mitogen Activated Protein Kinase ◽  
Receptor Interaction ◽  
Keratinocyte Proliferation ◽  
Skin Development

In order to enrich the Anser cygnoides genome and identify the gene expression profiles of primary and secondary feather follicles development, de novo transcriptome assembly of skin tissues was established by analyzing three developmental stages at embryonic day 14, 18, and 28 (E14, E18, E28). Sequencing output generated 436,730,608 clean reads from nine libraries and de novo assembled into 56,301 unigenes. There were 2,298, 9,423 and 12,559 unigenes showing differential expression in three stages respectively. Furthermore, differentially expressed genes (DEGs) were functionally classified according to genes ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and series-cluster analysis. Relevant specific GO terms such as epithelium development, regulation of keratinocyte proliferation, morphogenesis of an epithelium were identified. In all, 15,144 DEGs were clustered into eight profiles with distinct expression patterns and 2,424 DEGs were assigned to 198 KEGG pathways. Skin development related pathways (mitogen-activated protein kinase signaling pathway, extra-cellular matrix -receptor interaction, Wingless-type signaling pathway) and genes (delta like canonical Notch ligand 1, fibroblast growth factor 2, Snail family transcriptional repressor 2, bone morphogenetic protein 6, polo like kinase 1) were identified, and eight DEGs were selected to verify the reliability of transcriptome results by real-time quantitative PCR. The findings of this study will provide the key insights into the complicated molecular mechanism and breeding techniques underlying the developmental characteristics of skin and feather follicles in Anser cygnoides.

scholarly journals Innate, adaptive, and cell-autonomous immunity against Toxoplasma gondii infection

2019 ◽  
Vol 51 (12) ◽  
pp. 1-10 ◽  
Author(s):  
Miwa Sasai ◽  
Masahiro Yamamoto
Keyword(s):  
Immune Response ◽  
Toxoplasma Gondii ◽  
Immune Responses ◽  
Parasitophorous Vacuole ◽  
Interferon Γ ◽  
Protective Role ◽  
Ifn Γ ◽  
Acquired Immune Responses ◽  
Toxoplasma Gondii Infection ◽  
Antimicrobial Immunity

AbstractHosts have been fighting pathogens throughout the evolution of all infectious diseases. Toxoplasma gondii is one of the most common infectious agents in humans but causes only opportunistic infection in healthy individuals. Similar to antimicrobial immunity against other organisms, the immune response against T. gondii activates innate immunity and in turn induces acquired immune responses. After activation of acquired immunity, host immune cells robustly produce the proinflammatory cytokine interferon-γ (IFN-γ), which activates a set of IFN-γ-inducible proteins, including GTPases. IFN-inducible GTPases are essential for cell-autonomous immunity and are specialized for effective clearance and growth inhibition of T. gondii by accumulating in parasitophorous vacuole membranes. Recent studies suggest that the cell-autonomous immune response plays a protective role in host defense against not only T. gondii but also various intracellular bacteria. Moreover, the negative regulatory mechanisms of such strong immune responses are also important for host survival after infection. In this review, we will discuss in detail recent advances in the understanding of host defenses against T. gondii and the roles played by cell-autonomous immune responses.

Mining database for the therapeutic targets and prognostic biomarkers among STAT family in glioblastoma

2020 ◽  
pp. 1-13
Author(s):  
Chenglin Li ◽  
Yanfei Zhou ◽  
Hanshun Deng ◽  
Yuanshen Ye ◽  
Shuizhen Zhao ◽  
...  
Keyword(s):  
Immune Response ◽  
Signaling Pathway ◽  
Web Applications ◽  
Therapeutic Targets ◽  
Prognostic Biomarkers ◽  
Receptor Interaction ◽  
Immune Gene ◽  
Nf Kappa B ◽  
Signal Transducers ◽  
Pathways Analysis

BACKGROUND: Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor with a high mortality rate. Aberrant activation of signal transducers and activators of transcription (STAT) signaling results in tumor pathogenesis and progression by regulating cell cycle, cell survival and immune response. METHODS: Therapeutic targets and prognostic biomarkers within the STAT family in GBM were explored using web applications and databases. RESULTS: High levels of STAT1/3/5A/5B/6 and low levels of STAT4 were observed in GBM patients. GBM patients expressing high STAT1/2/3/5A/6 and low STAT4/5B levels had the worse overall survival. Among the STAT family, STAT4 and STAT6 were the most frequently mutated genes. A low to moderate correlation among members of the STAT family was observed. Additionally, the STATs were involved in activation or inhibition of cancer related pathways. Analysis of immune infiltrates showed STAT5A levels to be significantly correlated with abundance of immune cells and levels of immune gene biomarkers. Gene ontology (GO) functions and KEGG pathway analysis indicated that STAT5A is involved in immune response-regulating signaling pathway, neutrophil and lymphocyte mediated immunity, single-stranded DNA binding, cytokine-cytokine receptor interaction, NOD-like receptor signaling pathway, NF-kappa B signaling pathway and TNF signaling pathway. Moreover, several kinase and transcription factor targets of STAT5A in GBM were identified. CONCLUSION: We report here therapeutic targets, prognostic biomarkers and regulation network of STAT family in GBM. These findings lay a foundation for further studies on the role of STAT family in therapy and prognosis of GBM. Further studies are required to verify our results.

scholarly journals Comparative Gene Expression Analysis Reveals Similarities and Differences of Chronic Myeloid Leukemia Phases

Cancers ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 256
Author(s):  
Annemarie Schwarz ◽  
Ingo Roeder ◽  
Michael Seifert
Keyword(s):  
Gene Expression ◽  
Chronic Myeloid Leukemia ◽  
Signaling Pathway ◽  
Myeloid Leukemia ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Chronic Phase ◽  
Receptor Interaction ◽  
Similarities And Differences

Chronic myeloid leukemia (CML) is a slowly progressing blood cancer that primarily affects elderly people. Without successful treatment, CML progressively develops from the chronic phase through the accelerated phase to the blast crisis, and ultimately to death. Nowadays, the availability of targeted tyrosine kinase inhibitor (TKI) therapies has led to long-term disease control for the vast majority of patients. Nevertheless, there are still patients that do not respond well enough to TKI therapies and available targeted therapies are also less efficient for patients in accelerated phase or blast crises. Thus, a more detailed characterization of molecular alterations that distinguish the different CML phases is still very important. We performed an in-depth bioinformatics analysis of publicly available gene expression profiles of the three CML phases. Pairwise comparisons revealed many differentially expressed genes that formed a characteristic gene expression signature, which clearly distinguished the three CML phases. Signaling pathway expression patterns were very similar between the three phases but differed strongly in the number of affected genes, which increased with the phase. Still, significant alterations of MAPK, VEGF, PI3K-Akt, adherens junction and cytokine receptor interaction signaling distinguished specific phases. Our study also suggests that one can consider the phase-wise CML development as a three rather than a two-step process. This is in accordance with the phase-specific expression behavior of 24 potential major regulators that we predicted by a network-based approach. Several of these genes are known to be involved in the accumulation of additional mutations, alterations of immune responses, deregulation of signaling pathways or may have an impact on treatment response and survival. Importantly, some of these genes have already been reported in relation to CML (e.g., AURKB, AZU1, HLA-B, HLA-DMB, PF4) and others have been found to play important roles in different leukemias (e.g., CDCA3, RPL18A, PRG3, TLX3). In addition, increased expression of BCL2 in the accelerated and blast phase indicates that venetoclax could be a potential treatment option. Moreover, a characteristic signaling pathway signature with increased expression of cytokine and ECM receptor interaction pathway genes distinguished imatinib-resistant patients from each individual CML phase. Overall, our comparative analysis contributes to an in-depth molecular characterization of similarities and differences of the CML phases and provides hints for the identification of patients that may not profit from an imatinib therapy, which could support the development of additional treatment strategies.

Identification of key lncRNAs and mRNAs associated with Oral squamous cell carcinoma progression

2020 ◽  
Vol 15 ◽  
Author(s):  
Yong Mi ◽  
Na Li ◽  
Qing Li ◽  
Yang Shi ◽  
Congcong Zhang ◽  
...  
Keyword(s):  
Immune Response ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Squamous Cell ◽  
Differentially Expressed ◽  
Receptor Interaction ◽  
Type I ◽  
Catabolic Process

Background: Oral squamous cell carcinoma (OSCC) had been the sixth most common cancer worldwide. Emerging studies showed long non-coding RNAs played a key role in human cancers. However, the molecular mechanisms underlying the initiation and progression of OSCC remained to be further explored Objective: The present study aimed to identify differentially expressed lncRNAs and mRNAs in OSCC. Methods: GSE30784 was analyzed to identify differentially expressed lncRNAs and mRNAs in OSCC. Protein-protein interaction network and co-expression network analysis were performed to reveal the potential roles of OSCC related mRNAs and lncRNAs Results: In present study, we identified 21 up-regulated lncRNAs and 54 down-regulated lncRNAs in OSCC progression. Next we constructed a lncRNA related co-expression network in OSCC, which included 692 mRNAs and 2193 edges. Bioinformatics analysis showed lncRNAs were widely co-expressing with regulating type I interferon signaling pathway, extracellular matrix organization, collagen catabolic process, immune response, ECM-receptor interaction, Focal adhesion, and PI3K-Akt signaling pathway. A key network, included lncRNA C5orf66-AS1, C21orf15, LOC100506098, PCBP1-AS1, LOC284825, OR7E14P, HCG22, and FLG-AS1, were found to be involved in the regulation of immune response to tumor cell, Golgi calcium ion transport, negative regulation of vitamin D receptor signaling pathway, glycerol-3-phosphate catabolic process. Moreover, we found showed higher expression of CYP4F29P, PCBP1-AS1, HCG22, and C5orf66-AS1were associated with shorter overall survival time in OSCC samples Conclusions: We thought our analysis could provide novel insights to explore the potential mechanisms underlying OSCC progression

scholarly journals Identification of therapeutic targets and prognostic biomarkers among STAT family in glioblastoma

2020 ◽  
Author(s):  
Chenglin Li ◽  
Yanfei Zhou ◽  
Hanshun Deng ◽  
Yuanshen Ye ◽  
Shuizhen Zhao ◽  
...  
Keyword(s):  
Immune Response ◽  
Signaling Pathway ◽  
Web Applications ◽  
Therapeutic Targets ◽  
Prognostic Biomarkers ◽  
Receptor Interaction ◽  
Immune Gene ◽  
Kegg Pathways ◽  
Incidence And Mortality ◽  
Regulation Network

Abstract Background: Glioblastoma (GBM) is the most common and aggressive primary brain malignancies with high incidence and mortality. The aberrant activation of STAT signaling was confirmed to result in tumor pathogenesis and progress by regulating cell cycle, cell survival, and immune response. Methods: The clinical significance of and regulation network of STAT family in GBM were explored with several web applications or database. Results: The level of STAT1/3/5A/5B/6 were increased in GBM while STAT4 level was decreased. GBM patients with high expression of STAT1/2/3/5A/6 and low expression of STAT4/5B had a worse overall survival. Among the STAT family, STAT 4 and STAT6 were the top two frequently mutated genes. Correlation suggested a low to moderate correlation among STAT family. STAT family were also involved in the activation or inhibition of the famous cancer related pathways. Immune infiltrates analysis suggested that STAT5A level showed significantly correlated with the abundance of immune cells and the level of immune gene biomarkers. GO functions and KEGG pathways analysis revealed that STAT5A was involved in immune response-regulating signaling pathway, neutrophil and lymphocyte mediated immunity, single-stranded DNA binding, cytokine-cytokine receptor interaction, NOD-like receptor signaling pathway, NF-kappa B signaling pathway, and TNF signaling pathway. Moreover, we also identified several Kinase and transcription factor targets of STAT5A in GBM. Conclusions: Our results revealed the therapeutic targets, prognostic biomarkers and regulation network of STAT family in GBM, laying the foundation for further studies about STAT family in therapy and prognosis of GBM.

scholarly journals Mycobacterium tuberculosis LprE enhances bacterial persistence by inhibiting cathelicidin and autophagy in macrophages

2017 ◽  
Author(s):  
Avinash Padhi ◽  
Ella Bhagyaraj ◽  
Mehak Zahoor Khan ◽  
Mainak Biswas ◽  
Srabasti Sengupta ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Mycobacterium Tuberculosis ◽  
Immune Responses ◽  
Signaling Pathway ◽  
Mycobacterium Smegmatis ◽  
Bacterial Survival ◽  
Bacterial Persistence ◽  
Host Immune Responses ◽  
Mycobacterial Pathogenesis

ABSTRACTMycobacterium tuberculosis(Mtb)lipoproteins are known to facilitate bacterial survival by manipulating the host immune responses. Here, we have characterized a novelMtblipoprotein LprE(LprEMtb), and demonstrated its role in mycobacterial survival. LprEMtbacts by down-regulating the expression of cathelicidin, Cyp27B1, VDR and p38-MAPK via TLR-2 signaling pathway. Deletion oflprEMtbresulted in induction of cathelicidin and decreased survival in the host. Interestingly, LprEMtbwas also found to inhibit autophagy mechanism to dampen host immune response. Episomal expression of LprEMtbin non-pathogenicMycobacterium smegmatis(Msm) increased bacillary persistence by down-regulating the expression of cathelicidin and autophagy, while deletion of LprEMtborthologue inMsm, had no effect on cathelicidin and autophagy expression. Moreover, LprEMtbblocked phago-lysosome fusion by suppressing the expression of EEA1, Rab7 and LAMP-1 endosomal markers by down-regulating IL-12 and IL-22 cytokines. Our results indicate that LprEMtbplays an important role in mycobacterial pathogenesis in the context of innate immunity.

scholarly journals Integrative Omics Analysis Reveals the Immunomodulatory Effects of the Parasitic Dinoflagellate Hematodinium on Crustacean Immunity

2021 ◽  
Author(s):  
Meng Li ◽  
Qian Huang ◽  
Xiaoyang Lv ◽  
Hamish J. Small ◽  
Caiwen Li
Keyword(s):  
Immune Response ◽  
Signaling Pathway ◽  
Host Immune Response ◽  
Portunus Trituberculatus ◽  
Economic Losses ◽  
Receptor Interaction ◽  
Host Immune Responses ◽  
Humoral Immune ◽  
Host Parasite ◽  
Post Transcriptional Regulation

Parasitic dinoflagellates in genus Hematodinium have caused substantial economic losses to multiple commercially valuable marine crustaceans around the world. In the present study, comprehensive omics approaches (miRNA transcriptomics, iTRAQ-based proteomics) were applied to investigate the host-parasite interaction between hemocytes from Portunus trituberculatus and Hematodinium perezi. The parasitic dinoflagellate remodeled the miRNome and proteome of hemocytes from challenged hosts, modulated the host immune response at both post-transcriptional and translational levels and caused post-transcriptional regulation to the host immune response. Multiple important cellular and humoral immune-related pathways (ex. Apoptosis, Endocytosis, ECM-receptor interaction, proPO activation pathway, Toll-like signaling pathway, Jak-STAT signaling pathway) were significantly affected by Hematodinium parasites. Through modulation of the host miRNome, the host immune responses of nodulation, proPO activation and antimicrobial peptides were significantly suppressed. Cellular homeostasis was imbalanced via post-transcriptional dysregulation of the phagosome, peroxisome, and lysosome pathways. Cellular structure and communication was seriously impacted by post-transcriptional downregulation of ECM-receptor interaction and focal adhesion pathways.

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