scholarly journals The network interplay of interferon and Toll-like receptor signaling pathways in the anti-Candida immune response

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ranieri Coelho Salgado ◽  
Dennyson Leandro M. Fonseca ◽  
Alexandre H. C. Marques ◽  
Sarah Maria da Silva Napoleao ◽  
Tábata Takahashi França ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Fungal Infections ◽  
Meta Analysis ◽  
Expression Patterns ◽  
Integrative Approach ◽  
Toll Like Receptor ◽  
Specific Expression ◽  
Adaptive Immune Cells ◽  
Cell Type Specific Expression

AbstractFungal infections represent a major global health problem affecting over a billion people that kills more than 1.5 million annually. In this study, we employed an integrative approach to reveal the landscape of the human immune responses to Candida spp. through meta-analysis of microarray, bulk, and single-cell RNA sequencing (scRNA-seq) data for the blood transcriptome. We identified across these different studies a consistent interconnected network interplay of signaling molecules involved in both Toll-like receptor (TLR) and interferon (IFN) signaling cascades that is activated in response to different Candida species (C. albicans, C. auris, C. glabrata, C. parapsilosis, and C. tropicalis). Among these molecules are several types I IFN, indicating an overlap with antiviral immune responses. scRNA-seq data confirmed that genes commonly identified by the three transcriptomic methods show cell type-specific expression patterns in various innate and adaptive immune cells. These findings shed new light on the anti-Candida immune response, providing putative molecular pathways for therapeutic intervention.

scholarly journals The network interplay of interferon and toll-like receptor signaling pathways in the anti-Candida immune response

2021 ◽  
Author(s):  
Ranieri Coelho Salgado ◽  
Dennyson Leandro M. Fonseca ◽  
Alexandre H. C. Marques ◽  
Sarah M. S. Napoleao ◽  
Tabata Takahashi Franca ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Fungal Infections ◽  
Meta Analysis ◽  
Expression Patterns ◽  
Integrative Approach ◽  
Toll Like Receptor ◽  
Candida Spp ◽  
Specific Expression ◽  
Adaptive Immune Cells

Abstract Fungal infections represent a major global health problem that affects over a billion people and kills more than 1.5 million individuals annually. Here we employed an integrative approach to unravel the landscape of the human immune responses to Candida spp. by performing a meta-analysis of microarray, bulk, and single-cell RNA-sequencing (RNASeq) of blood transcriptome data. We identified across these different studies a consistent interconnected network interplay of signaling molecules involved in both toll-like receptor (TLR) and interferon (IFN) signaling cascades that is activated in response to different Candida species (C. albicans, C. auris, C. glabrata, C. parapsilosis, and C. tropicalis). Among these molecules, there are several types I IFN, indicating an overlap with the anti-viral immune responses. scRNAseq data confirmed that genes commonly identified by the three transcriptomic methods present a cell-type specific expression patterns across innate and adaptive immune cells. Thus, these data shed new lights on the anti-candida immune response, providing putative molecular pathways for therapeutic intervention.

scholarly journals The network interplay of interferon and toll-like receptor signaling pathways in the anti-Candida immune response

2021 ◽  
Author(s):  
Ranieri Coelho Salgado ◽  
Dennyson Leandro M. Fonseca ◽  
Alexandre H. C. Marques ◽  
Sarah Maria da Silva Napoleao ◽  
Tábata Takahashi França ◽  
...  
Keyword(s):  
Immune Response ◽  
Fungal Infections ◽  
Meta Analysis ◽  
Signaling Cascades ◽  
Integrative Approach ◽  
Toll Like Receptor ◽  
Candida Spp ◽  
Human Immune ◽  
Viral Responses ◽  
Blood Transcriptome

Abstract Fungal infections represent a major global health problem that affects over a billion people and kills more than 1.5 million individuals annually. Here we employed an integrative approach to unravel the landscape of the human immune responses to Candida spp. (C. albicans and C. auris) by performing a meta-analysis of microarray, bulk, and single-cell RNA-sequencing (RNASeq) of blood transcriptome data. We identified that C. albicans activates a network interplay of signaling molecules commonly involved in both toll-like receptor (TLR) and interferon (IFN) signaling cascades. These molecules form a highly interconnected interferome network, which contains an immune overlap with the anti-viral responses. scRNAseq data confirmed that genes commonly identified by the three transcriptomic methods present a consistent upregulation pattern across innate immune and adaptive cells (CD4+, CD8+, and CD19+ lymphocytes). Thus, our results shed new lights on the molecular basis of immune response to Candida spp.

scholarly journals Cell-type Specific Expression Quantitative Trait Loci Associated with Alzheimer Disease in Blood and Brain Tissue

2020 ◽  
Author(s):  
Devanshi Patel ◽  
Xiaoling Zhang ◽  
John J. Farrell ◽  
Jaeyoon Chung ◽  
Thor D. Stein ◽  
...  
Keyword(s):  
Gene Expression ◽  
Quantitative Trait ◽  
Expression Patterns ◽  
Regulation Of Gene Expression ◽  
Cell Types ◽  
Eqtl Analysis ◽  
Cell Type ◽  
Specific Expression ◽  
Cell Type Specific Expression ◽  
Cell Type Specific

ABSTRACTBecause regulation of gene expression is heritable and context-dependent, we investigated AD-related gene expression patterns in cell-types in blood and brain. Cis-expression quantitative trait locus (eQTL) mapping was performed genome-wide in blood from 5,257 Framingham Heart Study (FHS) participants and in brain donated by 475 Religious Orders Study/Memory & Aging Project (ROSMAP) participants. The association of gene expression with genotypes for all cis SNPs within 1Mb of genes was evaluated using linear regression models for unrelated subjects and linear mixed models for related subjects. Cell type-specific eQTL (ct-eQTL) models included an interaction term for expression of “proxy” genes that discriminate particular cell type. Ct-eQTL analysis identified 11,649 and 2,533 additional significant gene-SNP eQTL pairs in brain and blood, respectively, that were not detected in generic eQTL analysis. Of note, 386 unique target eGenes of significant eQTLs shared between blood and brain were enriched in apoptosis and Wnt signaling pathways. Five of these shared genes are established AD loci. The potential importance and relevance to AD of significant results in myeloid cell-types is supported by the observation that a large portion of GWS ct-eQTLs map within 1Mb of established AD loci and 58% (23/40) of the most significant eGenes in these eQTLs have previously been implicated in AD. This study identified cell-type specific expression patterns for established and potentially novel AD genes, found additional evidence for the role of myeloid cells in AD risk, and discovered potential novel blood and brain AD biomarkers that highlight the importance of cell-type specific analysis.

scholarly journals Assessment of humoral and cell-mediated immune responses to pertussis vaccination: a systematic review protocol

BMJ Open ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. e028109 ◽  
Author(s):  
Funbi Akinola ◽  
Rudzani Muloiwa ◽  
Gregory, D Hussey ◽  
Violette Dirix ◽  
Benjamin Kagina ◽  
...  
Keyword(s):  
Systematic Review ◽  
Immune Response ◽  
Immune Responses ◽  
Public Space ◽  
Systematic Reviews ◽  
Data Extraction ◽  
Meta Analysis ◽  
Grey Literature ◽  
Assessment Tools ◽  
Population Type

IntroductionGlobally, some studies show a resurgence of pertussis. The risks and benefits of using whole-cell pertussis (wP) or acellular pertussis (aP) vaccines in the control of the disease have been widely debated. Better control of pertussis will require improved understanding of the immune response to pertussis vaccines. Improved understanding and assessment of the immunity induced by pertussis vaccines is thus imperative. Several studies have documented different immunological outcomes to pertussis vaccination from an array of assays. We propose to conduct a systematic review of the different immunological assays and outcomes used in the assessment of the humoraland cell-mediated immune response following pertussis vaccination.Methods and analysisThe primary outcomes for consideration are quality and quantity of immune responses (humoral and cell-mediated) post-pertussis vaccination. Of interest as secondary outcomes are types of immunoassays used in assessing immune responses post-pertussis vaccination, types of biological samples used in assessing immune responses post-pertussis vaccination, as well as the types of antigens used to stimulate these samples during post-pertussis vaccination immune response assessments. Different electronic databases (including PubMed, Cochrane, EBSCO Host, Scopus and Web of Science) will be accessed for peer-reviewed published and grey literature evaluating immune responses to pertussis vaccines between 1990 and 2019. The quality of included articles will be assessed using standardised risk and quality assessment tools specific to the study design used in each article. Data extraction will be done using a data extraction form. The extracted data will be analysed using STATA V.14.0 and RevMan V.5.3 software. A subgroup analysis will be conducted based on the study population, type of vaccine (wP or aP) and type of immune response (cell-mediated or humoral). Guidelines for reporting systematic reviews in the revised 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement will be used in this study.Ethics and disseminationEthics approval is not required for this study as it is a systematic review. We will only make use of data already available in the public space. Findings will be reported via publication in a peer-reviewed journal and presented at scientific meetings and workshops.Trial registration numberCRD42018102455.

scholarly journals Dual Role of Toll-Like Receptor 7 in the Pathogenesis of Rabies Virus in a Mouse Model

2020 ◽  
Vol 94 (9) ◽  
Author(s):  
Zhaochen Luo ◽  
Lei Lv ◽  
Yingying Li ◽  
Baokun Sui ◽  
Qiong Wu ◽  
...  
Keyword(s):  
Immune Response ◽  
Mouse Model ◽  
Immune Responses ◽  
Rabies Virus ◽  
Mouse Brain ◽  
Early Stage ◽  
Toll Like Receptor ◽  
Innate Recognition ◽  
Recognition Receptor

ABSTRACT Rabies, caused by rabies virus (RABV), is a fatal encephalitis in humans and other mammals, which continues to present a public health threat in most parts of the world. Our previous study demonstrated that Toll-like receptor 7 (TLR7) is essential in the induction of anti-RABV antibodies via the facilitation of germinal center formation. In the present study, we investigated the role of TLR7 in the pathogenicity of RABV in a mouse model. Using isolated plasmacytoid dendritic cells (pDCs), we demonstrated that TLR7 is an innate recognition receptor for RABV. When RABV invaded from the periphery, TLR7 detected viral single-stranded RNA and triggered immune responses that limited the virus’s entry into the central nervous system (CNS). When RABV had invaded the CNS, its detection by TLR7 led to the production of cytokines and chemokines and an increase the permeability of the blood-brain barrier. Consequently, peripheral immune cells, including pDCs, macrophages, neutrophils, and B cells infiltrated the CNS. While this immune response, triggered by TLR7, helped to clear viruses, it also increased neuroinflammation and caused immunopathology in the mouse brain. Our results demonstrate that TLR7 is an innate recognition receptor for RABV, which restricts RABV invasion into the CNS in the early stage of viral infection but also contributes to immunopathology by inducing neuroinflammation. IMPORTANCE Developing targeted treatment for RABV requires understanding the innate immune response to the virus because early virus clearance is essential for preventing the fatality when the infection has progressed to the CNS. Previous studies have revealed that TLR7 is involved in the immune response to RABV. Here, we establish that TLR7 recognizes RABV and facilitates the production of some interferon-stimulated genes. We also demonstrated that when RABV invades into the CNS, TLR7 enhances the production of inflammatory cytokines which contribute to immunopathology in the mouse brain. Taken together, our findings suggest that treatments for RABV must consider the balance between the beneficial and harmful effects of TLR7-triggered immune responses.

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 Impact of Toll-Like Receptor-Specific Agonists on the Host Immune Response to the Yersinia pestis Plague rF1V Vaccine

2021 ◽  
Vol 12 ◽  
Author(s):  
Sergei Biryukov ◽  
Jennifer L. Dankmeyer ◽  
Zain Shamsuddin ◽  
Ivan Velez ◽  
Nathaniel O. Rill ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Fusion Protein ◽  
Yersinia Pestis ◽  
Vaccine Efficacy ◽  
Host Immune Response ◽  
Toll Like Receptor ◽  
Vaccine Strategy ◽  
Pneumonic Plague ◽  
Plague Vaccine

Relatively recent advances in plague vaccinology have produced the recombinant fusion protein F1-V plague vaccine. This vaccine has been shown to readily protect mice from both bubonic and pneumonic plague. The protection afforded by this vaccine is solely based upon the immune response elicited by the F1 or V epitopes expressed on the F1-V fusion protein. Accordingly, questions remain surrounding its efficacy against infection with non-encapsulated (F1-negative) strains. In an attempt to further optimize the F1-V elicited immune response and address efficacy concerns, we examined the inclusion of multiple toll-like receptor agonists into vaccine regimens. We examined the resulting immune responses and also any protection afforded to mice that were exposed to aerosolized Yersinia pestis. Our data demonstrate that it is possible to further augment the F1-V vaccine strategy in order to optimize and augment vaccine efficacy.

scholarly journals Transcriptome, Spliceosome and Editome Expression Patterns of the Porcine Endometrium in Response to a Single Subclinical Dose of Salmonella Enteritidis Lipopolysaccharide

2020 ◽  
Vol 21 (12) ◽  
pp. 4217
Author(s):  
Lukasz Paukszto ◽  
Anita Mikolajczyk ◽  
Jan P. Jastrzebski ◽  
Marta Majewska ◽  
Kamil Dobrzyn ◽  
...  
Keyword(s):  
Immune Response ◽  
Rna Editing ◽  
Salmonella Enteritidis ◽  
Clinical Symptoms ◽  
Expression Patterns ◽  
Noncoding Rnas ◽  
Variant Calling ◽  
Long Noncoding Rnas ◽  
Specific Expression

Endometrial infections at a young age can lead to fertility issues in adulthood. Bacterial endotoxins, such as lipopolysaccharide (LPS), can participate in long-term molecular changes even at low concentrations. Lipopolysaccharide plays a crucial role in the progression of septic shock, inflammation and auto-immune diseases. The aim of this study was to describe transcriptomic modulations in the porcine endometrium, induced in vivo by a single subclinical dose of LPS from Salmonella Enteritidis. which did not produce clinical symptoms of toxicity. The RNA-seq methodology was applied to reveal 456 differentially expressed regions, including 375 genes, four long noncoding RNAs, and 77 other unclassified transcripts. Two independent methods confirmed 118 alternatively spliced genes that participate i.a., in the formation of the MHC-I complex and the adaptive immune response. Single nucleotide variant-calling algorithms supported the identification of 3730 allele-specific expression variants and 57 canonical A-to-I RNA editing sites. The results demonstrated that the differential expression of genes involved in inflammation, immune response, angiogenesis and endometrial development may be maintained for up to 7 days after exposure to LPS. RNA editing sites and long noncoding RNAs (lncRNAs) play an important role in transcriptional regulatory machinery in the porcine endometrium in response to LPS administration.

scholarly journals Systems and Synthetic microRNA Biology: From Biogenesis to Disease Pathogenesis

2019 ◽  
Vol 21 (1) ◽  
pp. 132 ◽  
Author(s):  
Hironori Matsuyama ◽  
Hiroshi I. Suzuki
Keyword(s):  
Expression Patterns ◽  
System Level ◽  
Mirna Biogenesis ◽  
Mirna Regulation ◽  
Specific Expression ◽  
Synthetic Gene Circuits ◽  
Mirna Genes ◽  
Super Enhancer ◽  
Cell Type Specific Expression ◽  
And Function

MicroRNAs (miRNAs) are approximately 22-nucleotide-long, small non-coding RNAs that post-transcriptionally regulate gene expression. The biogenesis of miRNAs involves multiple steps, including the transcription of primary miRNAs (pri-miRNAs), nuclear Drosha-mediated processing, cytoplasmic Dicer-mediated processing, and loading onto Argonaute (Ago) proteins. Further, miRNAs control diverse biological and pathological processes via the silencing of target mRNAs. This review summarizes recent findings regarding the quantitative aspects of miRNA homeostasis, including Drosha-mediated pri-miRNA processing, Ago-mediated asymmetric miRNA strand selection, and modifications of miRNA pathway components, as well as the roles of RNA modifications (epitranscriptomics), epigenetics, transcription factor circuits, and super-enhancers in miRNA regulation. These recent advances have facilitated a system-level understanding of miRNA networks, as well as the improvement of RNAi performance for both gene-specific targeting and genome-wide screening. The comprehensive understanding and modeling of miRNA biogenesis and function have been applied to the design of synthetic gene circuits. In addition, the relationships between miRNA genes and super-enhancers provide the molecular basis for the highly biased cell type-specific expression patterns of miRNAs and the evolution of miRNA–target connections, while highlighting the importance of alterations of super-enhancer-associated miRNAs in a variety of human diseases.

scholarly journals Differential induction of Pax genes by NGF and BDNF in cerebellar primary cultures.

1994 ◽  
Vol 125 (2) ◽  
pp. 417-425 ◽  
Author(s):  
C Kioussi ◽  
P Gruss
Keyword(s):  
Gene Family ◽  
Expression Patterns ◽  
Primary Cultures ◽  
Neuronal Cell ◽  
Cell Types ◽  
Early Gene ◽  
Specific Expression ◽  
Pax Genes ◽  
Cell Type Specific Expression

The Pax genes encode sequence-specific DNA binding transcription factors that are expressed in embryonic development of the nervous system. Primary neuronal cell cultures derived from the cerebellar cortex of embryonic day 14, newborn and 7-d old mice, were used to investigate the cell-type specific expression patterns of three members of the murine paired box containing gene family (Pax gene family), in vitro. Cell types which express Pax-2, Pax-3, and Pax-6 RNA in primary cultures correspond to those found in regions of the cerebellum which show RNA signals in sections of the developing mouse brain. To find mechanisms regulating Pax gene expression during cerebellar development, the differential regulation of Pax-2, Pax-3, and Pax-6 by NGF and BDNF, two structurally related neurotrophins, was studied in such primary cultures. Pax-2 and Pax-6 RNA increased slightly by 1 h and remained elevated throughout a 24-h treatment with BDNF and NGF. Pax-3 RNA was not detected in newborn cultures, but underwent a rapid (1 h) and transient (2 h) induction upon treatment with either BDNF or NGF. No response was seen with EGF or FGF. Cycloheximide treatment amplified Pax-3 induction and prolonged the signal. Thus, Pax-3 induction resembles that of the immediate-early gene c-fos, which transduces growth factor signals during the development of particular neuronal/glial cell types. The changes in Pax expression were inductive rather than trophic.

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