scholarly journals Dual RNA-seq transcriptome analysis of caecal tissue during primary Eimeria tenella infection in chickens

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Arnar K. S. Sandholt ◽  
Eva Wattrang ◽  
Tobias Lilja ◽  
Harri Ahola ◽  
Anna Lundén ◽  
...  
Keyword(s):  
Negative Impact ◽  
Host Responses ◽  
Enteric Infection ◽  
Host Immune System ◽  
Rna Seq ◽  
Altered Expression ◽  
Immune Genes ◽  
Dna And Rna ◽  
Ifn Γ ◽  
Regulatory Effects

Abstract Background Coccidiosis is an infectious disease with large negative impact on the poultry industry worldwide. It is an enteric infection caused by unicellular Apicomplexan parasites of the genus Eimeria. The present study aimed to gain more knowledge about interactions between parasites and the host immune system during the early asexual replication phase of E. tenella in chicken caeca. For this purpose, chickens were experimentally infected with E. tenella oocysts, sacrificed on days 1–4 and 10 after infection and mRNA from caecal tissues was extracted and sequenced. Results Dual RNA-seq analysis revealed time-dependent changes in both host and parasite gene expression during the course of the infection. Chicken immune activation was detected from day 3 and onwards with the highest number of differentially expressed immune genes recorded on day 10. Among early (days 3–4) responses up-regulation of genes for matrix metalloproteinases, several chemokines, interferon (IFN)-γ along with IFN-stimulated genes GBP, IRF1 and RSAD2 were noted. Increased expression of genes with immune suppressive/regulatory effects, e.g. IL10, SOCS1, SOCS3, was also observed among early responses. For E. tenella a general up-regulation of genes involved in protein expression and energy metabolism as well as a general down-regulation genes for DNA and RNA processing were observed during the infection. Specific E. tenella genes with altered expression during the experiment include those for proteins in rhoptry and microneme organelles. Conclusions The present study provides novel information on both the transcriptional activity of E. tenella during schizogony in ceacal tissue and of the local host responses to parasite invasion during this phase of infection. Results indicate a role for IFN-γ and IFN-stimulated genes in the innate defence against Eimeria replication.

scholarly journals Lessons from Toxoplasma: Host responses that mediate parasite control and the microbial effectors that subvert them

2021 ◽  
Vol 218 (11) ◽  
Author(s):  
Eva-Maria Frickel ◽  
Christopher A. Hunter
Keyword(s):  
Immune System ◽  
Toxoplasma Gondii ◽  
Experimental System ◽  
Host Responses ◽  
Host Immune System ◽  
Intracellular Parasite ◽  
Parasite Control ◽  
Host Pathogen ◽  
Ifn Γ ◽  
Intracellular Infections

The intracellular parasite Toxoplasma gondii has long provided a tractable experimental system to investigate how the immune system deals with intracellular infections. This review highlights the advances in defining how this organism was first detected and the studies with T. gondii that contribute to our understanding of how the cytokine IFN-γ promotes control of vacuolar pathogens. In addition, the genetic tractability of this eukaryote organism has provided the foundation for studies into the diverse strategies that pathogens use to evade antimicrobial responses and now provides the opportunity to study the basis for latency. Thus, T. gondii remains a clinically relevant organism whose evolving interactions with the host immune system continue to teach lessons broadly relevant to host–pathogen interactions.

scholarly journals Long noncoding RNAs are involved in multiple immunological pathways in response to vaccination

2019 ◽  
Vol 116 (34) ◽  
pp. 17121-17126 ◽  
Author(s):  
Diógenes S. de Lima ◽  
Lucas E. Cardozo ◽  
Vinicius Maracaja-Coutinho ◽  
Andreas Suhrbier ◽  
Karim Mane ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Host Responses ◽  
Biological Processes ◽  
Rna Seq ◽  
Altered Expression ◽  
Live Attenuated Influenza Vaccine ◽  
Induced Immunity ◽  
Blood Transcriptome

Understanding the mechanisms of vaccine-elicited protection contributes to the development of new vaccines. The emerging field of systems vaccinology provides detailed information on host responses to vaccination and has been successfully applied to study the molecular mechanisms of several vaccines. Long noncoding RNAs (lncRNAs) are crucially involved in multiple biological processes, but their role in vaccine-induced immunity has not been explored. We performed an analysis of over 2,000 blood transcriptome samples from 17 vaccine cohorts to identify lncRNAs potentially involved with antibody responses to influenza and yellow fever vaccines. We have created an online database where all results from this analysis can be accessed easily. We found that lncRNAs participate in distinct immunological pathways related to vaccine-elicited responses. Among them, we showed that the expression of lncRNA FAM30A was high in B cells and correlates with the expression of immunoglobulin genes located in its genomic vicinity. We also identified altered expression of these lncRNAs in RNA-sequencing (RNA-seq) data from a cohort of children following immunization with intranasal live attenuated influenza vaccine, suggesting a common role across several diverse vaccines. Taken together, these findings provide evidence that lncRNAs have a significant impact on immune responses induced by vaccination.

scholarly journals CCL19 enhances CD8+ T-cell responses and accelerates HBV clearance

2021 ◽  
Author(s):  
Yan Yan ◽  
Wei Zhao ◽  
Wei Liu ◽  
Yan Li ◽  
Xu Wang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Crucial Role ◽  
Cell Activation ◽  
Hbv Infection ◽  
Host Immune System ◽  
Tnf Α ◽  
Ifn Γ ◽  
High Level

Abstract Background Chemokine (C–C motif) ligand 19 (CCL19) is a leukocyte chemoattractant that plays a crucial role in cell trafficking and leukocyte activation. Dysfunctional CD8+ T cells play a crucial role in persistent HBV infection. However, whether HBV can be cleared by CCL19-activated immunity remains unclear. Methods We assessed the effects of CCL19 on the activation of PBMCs in patients with HBV infection. We also examined how CCL19 influences HBV clearance and modulates HBV-responsive T cells in a mouse model of chronic hepatitis B (CHB). In addition, C–C chemokine-receptor type 7 (CCR7) knockdown mice were used to elucidate the underlying mechanism of CCL19/CCR7 axis-induced immune activation. Results From in vitro experiments, we found that CCL19 enhanced the frequencies of Ag-responsive IFN-γ+ CD8+ T cells from patients by approximately twofold, while CCR7 knockdown (LV-shCCR7) and LY294002 partially suppressed IFN-γ secretion. In mice, CCL19 overexpression led to rapid clearance of intrahepatic HBV likely through increased intrahepatic CD8+ T-cell proportion, decreased frequency of PD-1+ CD8+ T cells in blood and compromised suppression of hepatic APCs, with lymphocytes producing a significantly high level of Ag-responsive TNF-α and IFN-γ from CD8+ T cells. In both CCL19 over expressing and CCR7 knockdown (AAV-shCCR7) CHB mice, the frequency of CD8+ T-cell activation-induced cell death (AICD) increased, and a high level of Ag-responsive TNF-α and low levels of CD8+ regulatory T (Treg) cells were observed. Conclusions Findings in this study provide insights into how CCL19/CCR7 axis modulates the host immune system, which may promote the development of immunotherapeutic strategies for HBV treatment by overcoming T-cell tolerance.

scholarly journals Characterization of nucleic acids from extracellular vesicle-enriched human sweat

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Geneviève Bart ◽  
Daniel Fischer ◽  
Anatoliy Samoylenko ◽  
Artem Zhyvolozhnyi ◽  
Pavlo Stehantsev ◽  
...  
Keyword(s):  
Nucleic Acids ◽  
Human Genome ◽  
Body Fluids ◽  
Lower Percentage ◽  
Rna Seq ◽  
Protein Coding ◽  
Human Sweat ◽  
Dna And Rna ◽  
Ribonucleoprotein Complexes ◽  
Eccrine Glands

Abstract Background The human sweat is a mixture of secretions from three types of glands: eccrine, apocrine, and sebaceous. Eccrine glands open directly on the skin surface and produce high amounts of water-based fluid in response to heat, emotion, and physical activity, whereas the other glands produce oily fluids and waxy sebum. While most body fluids have been shown to contain nucleic acids, both as ribonucleoprotein complexes and associated with extracellular vesicles (EVs), these have not been investigated in sweat. In this study we aimed to explore and characterize the nucleic acids associated with sweat particles. Results We used next generation sequencing (NGS) to characterize DNA and RNA in pooled and individual samples of EV-enriched sweat collected from volunteers performing rigorous exercise. In all sequenced samples, we identified DNA originating from all human chromosomes, but only the mitochondrial chromosome was highly represented with 100% coverage. Most of the DNA mapped to unannotated regions of the human genome with some regions highly represented in all samples. Approximately 5 % of the reads were found to map to other genomes: including bacteria (83%), archaea (3%), and virus (13%), identified bacteria species were consistent with those commonly colonizing the human upper body and arm skin. Small RNA-seq from EV-enriched pooled sweat RNA resulted in 74% of the trimmed reads mapped to the human genome, with 29% corresponding to unannotated regions. Over 70% of the RNA reads mapping to an annotated region were tRNA, while misc. RNA (18,5%), protein coding RNA (5%) and miRNA (1,85%) were much less represented. RNA-seq from individually processed EV-enriched sweat collection generally resulted in fewer percentage of reads mapping to the human genome (7–45%), with 50–60% of those reads mapping to unannotated region of the genome and 30–55% being tRNAs, and lower percentage of reads being rRNA, LincRNA, misc. RNA, and protein coding RNA. Conclusions Our data demonstrates that sweat, as all other body fluids, contains a wealth of nucleic acids, including DNA and RNA of human and microbial origin, opening a possibility to investigate sweat as a source for biomarkers for specific health parameters.

scholarly journals SLAMF7 engagement super-activates macrophages in acute and chronic inflammation

2020 ◽  
Author(s):  
Daimon P. Simmons ◽  
Hung N. Nguyen ◽  
Emma Gomez-Rivas ◽  
Yunju Jeong ◽  
Antonia F. Chen ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Immune Responses ◽  
Inflammatory Cytokine ◽  
Macrophage Activation ◽  
Rna Seq ◽  
Autocrine Signaling ◽  
Tnf Α ◽  
Activated Macrophage ◽  
Ifn Γ ◽  
Acute And Chronic Inflammation

AbstractMacrophages regulate protective immune responses to infectious microbes, but aberrant macrophage activation frequently drives pathological inflammation. To identify regulators of vigorous macrophage activation, we analyzed RNA-seq data from synovial macrophages and identified SLAMF7 as a receptor associated with a super-activated macrophage state in rheumatoid arthritis. We implicated IFN-γ as a key regulator of SLAMF7 expression. Engaging this receptor drove an exuberant wave of inflammatory cytokine expression, and induction of TNF-α following SLAMF7 engagement amplified inflammation through an autocrine signaling loop. We observed SLAMF7-induced gene programs not only in macrophages from rheumatoid arthritis patients, but in gut macrophages from active Crohn’s disease patients and lung macrophages from severe COVID-19 patients. This suggests a central role for SLAMF7 in macrophage super-activation with broad implications in pathology.

scholarly journals Meta-Analysis: Randomized Trials of Lactobacillus plantarum on Immune Regulation Over the Last Decades

2021 ◽  
Vol 12 ◽  
Author(s):  
Wei Zhao ◽  
Chuantao Peng ◽  
Hafiz Arbab Sakandar ◽  
Lai-Yu Kwok ◽  
Wenyi Zhang
Keyword(s):  
Meta Analysis ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Central Register ◽  
Tnf Α ◽  
Ifn Γ ◽  
The Mean ◽  
Regulatory Effects ◽  
Mean Differences ◽  
Necrosis Factor

Lactobacillus (L.) plantarum strains, belong to lactic acid bacteria group, are considered indispensable probiotics. Here, we performed meta-analysis to evaluate the regulatory effects of L. plantarum on the immunity during clinical trials. This meta-analysis was conducted by searching across four most common literature databases, namely, Cochrane Central Register of Controlled Trials, Web of Science, Embase, and PubMed. Clinical trial articles that met the inclusion and exclusion criteria were analyzed by Review Manager (version 5.3). p-value < 0.05 of the total effect was considered statistically significant. Finally, total of 677 references were retrieved, among which six references and 18 randomized controlled trials were included in the meta-analysis. The mean differences observed at 95% confidence interval: interleukin (IL)-4, −0.48 pg/mL (−0.79 to −0.17; p < 0.05); IL-10, 9.88 pg/mL (6.52 to 13.2; p < 0.05); tumor necrosis factor (TNF)-α, −2.34 pg/mL (−3.5 to −1.19; p < 0.05); interferon (IFN)-γ, −0.99 pg/mL (−1.56 to −0.41; p < 0.05). Therefore, meta-analysis results suggested that L. plantarum could promote host immunity by regulating pro-inflammatory and anti-inflammatory cytokines.

scholarly journals Targeting Neoepitopes to Treat Solid Malignancies: Immunosurgery

2021 ◽  
Vol 12 ◽  
Author(s):  
Eric de Sousa ◽  
Joana R. Lérias ◽  
Antonio Beltran ◽  
Georgia Paraschoudi ◽  
Carolina Condeço ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Human Leukocyte ◽  
Immune Checkpoint Blockade ◽  
Successful Outcome ◽  
Clinical Samples ◽  
Cancer Tissue ◽  
Rna Seq ◽  
Peripheral T Cells ◽  
Ifn Γ

Successful outcome of immune checkpoint blockade in patients with solid cancers is in part associated with a high tumor mutational burden (TMB) and the recognition of private neoantigens by T-cells. The quality and quantity of target recognition is determined by the repertoire of ‘neoepitope’-specific T-cell receptors (TCRs) in tumor-infiltrating lymphocytes (TIL), or peripheral T-cells. Interferon gamma (IFN-γ), produced by T-cells and other immune cells, is essential for controlling proliferation of transformed cells, induction of apoptosis and enhancing human leukocyte antigen (HLA) expression, thereby increasing immunogenicity of cancer cells. TCR αβ-dependent therapies should account for tumor heterogeneity and availability of the TCR repertoire capable of reacting to neoepitopes and functional HLA pathways. Immunogenic epitopes in the tumor-stroma may also be targeted to achieve tumor-containment by changing the immune-contexture in the tumor microenvironment (TME). Non protein-coding regions of the tumor-cell genome may also contain many aberrantly expressed, non-mutated tumor-associated antigens (TAAs) capable of eliciting productive anti-tumor immune responses. Whole-exome sequencing (WES) and/or RNA sequencing (RNA-Seq) of cancer tissue, combined with several layers of bioinformatic analysis is commonly used to predict possible neoepitopes present in clinical samples. At the ImmunoSurgery Unit of the Champalimaud Centre for the Unknown (CCU), a pipeline combining several tools is used for predicting private mutations from WES and RNA-Seq data followed by the construction of synthetic peptides tailored for immunological response assessment reflecting the patient’s tumor mutations, guided by MHC typing. Subsequent immunoassays allow the detection of differential IFN-γ production patterns associated with (intra-tumoral) spatiotemporal differences in TIL or peripheral T-cells versus TIL. These bioinformatics tools, in addition to histopathological assessment, immunological readouts from functional bioassays and deep T-cell ‘adaptome’ analyses, are expected to advance discovery and development of next-generation personalized precision medicine strategies to improve clinical outcomes in cancer in the context of i) anti-tumor vaccination strategies, ii) gauging mutation-reactive T-cell responses in biological therapies and iii) expansion of tumor-reactive T-cells for the cellular treatment of patients with cancer.

scholarly journals BRPF3 knockdown or inhibition moderately reverses olaparib resistance in high grade serous ovarian carcinoma, but depletion of H3K14 acetylation has no effect

2021 ◽  
Author(s):  
Benjamin G Bitler ◽  
Tomomi M Yamamoto ◽  
Alexandra McMellen ◽  
Hyunmin Kim ◽  
Zachary Levi Watson
Keyword(s):  
Dna Repair ◽  
Ovarian Carcinoma ◽  
Clinical Problem ◽  
Parp Inhibitors ◽  
High Grade ◽  
Rna Seq ◽  
Damage Resistance ◽  
Altered Expression ◽  
Serous Ovarian Carcinoma ◽  
H3k14 Acetylation

Background: PARP inhibitors (PARPi) kill cancer cells by stalling DNA replication and preventing DNA repair, resulting in a critical accumulation of DNA damage. Resistance to PARPi is a growing clinical problem in the treatment of high grade serous ovarian carcinoma (HGSOC). Acetylation of histone H3 lysine 14 (H3K14ac) and associated histone acetyltransferases (HATs) have known functions in DNA repair and replication, but their expression and activities have not been examined in the context of PARPi-resistant HGSOC. Results: Using mass spectrometry profiling of histone modifications, we observed altered H3K14ac enrichment in PARPi-resistant HGSOC cells relative to isogenic PARPi-sensitive lines. By RT-qPCR and RNA-Seq, we also observed altered expression of numerous HATs in PARPi-resistant HGSOC cells and a PARPi-resistant PDX model. Knockdown of HATs only modestly altered PARPi response, although knockdown and inhibition of PCAF significantly increased resistance. Pharmacologic inhibition of HBO1 severely depleted H3K14ac but did not affect PARPi response. However, knockdown and inhibition of BRPF3, which is known to interact in a complex with HBO1, did reduce PARPi resistance. Conclusions: This study demonstrates that severe depletion of H3K14ac does not affect PARPi response in HGSOC. Our data suggest that bromodomain functions of HAT proteins such as PCAF, or accessory proteins such as BRPF3, may play a greater role in PARPi response than acetyltransferase functions.

scholarly journals Cleavage of DNA and RNA by PLD3 and PLD4 limits autoinflammatory triggering by multiple sensors

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Amanda L. Gavin ◽  
Deli Huang ◽  
Tanya R. Blane ◽  
Therese C. Thinnes ◽  
Yusuke Murakami ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Inflammatory Diseases ◽  
Type I ◽  
Multiple Sensors ◽  
Dna And Rna ◽  
Elevated Type ◽  
Minor Contribution ◽  
Ifn Γ ◽  
A Minor ◽  
Rna And Dna

AbstractPhospholipase D3 (PLD3) and PLD4 polymorphisms have been associated with several important inflammatory diseases. Here, we show that PLD3 and PLD4 digest ssRNA in addition to ssDNA as reported previously. Moreover, Pld3−/−Pld4−/− mice accumulate small ssRNAs and develop spontaneous fatal hemophagocytic lymphohistiocytosis (HLH) characterized by inflammatory liver damage and overproduction of Interferon (IFN)-γ. Pathology is rescued in Unc93b13d/3dPld3−/−Pld4−/− mice, which lack all endosomal TLR signaling; genetic codeficiency or antibody blockade of TLR9 or TLR7 ameliorates disease less effectively, suggesting that both RNA and DNA sensing by TLRs contributes to inflammation. IFN-γ made a minor contribution to pathology. Elevated type I IFN and some other remaining perturbations in Unc93b13d/3dPld3−/−Pld4−/− mice requires STING (Tmem173). Our results show that PLD3 and PLD4 regulate both endosomal TLR and cytoplasmic/STING nucleic acid sensing pathways and have implications for the treatment of nucleic acid-driven inflammatory disease.

scholarly journals A Cell Atlas of Microbe-Responsive Processes in the Zebrafish Intestine

2020 ◽  
Author(s):  
Reegan J. Willms ◽  
Jennifer C. Hocking ◽  
Edan Foley
Keyword(s):  
Transcriptional Activity ◽  
Cell Types ◽  
Cellular Heterogeneity ◽  
Host Responses ◽  
Cellular Specificity ◽  
Direct Growth ◽  
A Cell ◽  
Microbe Interactions ◽  
Regulatory Effects ◽  
Host Microbe Interactions

ABSTRACTGut microbial products direct growth, differentiation and development in the animal host. Disruptions to host-microbe interactions have profound health consequences, that include onset of chronic inflammatory illnesses. However, we lack system-wide understanding of cell-specific responses to the microbiome. We profiled transcriptional activity in individual cells from the intestine, and associated tissue, of zebrafish larvae that we raised in the presence, or absence, of a microbiome. We uncovered extensive cellular heterogeneity in the conventional zebrafish intestinal epithelium, including previously undescribed cell types with known mammalian homologs. By comparing conventional to germ-free profiles, we mapped microbial impacts on transcriptional activity in each cell population. We revealed intricate degrees of cellular specificity in host responses to the microbiome, that included regulatory effects on patterning, metabolic and immune activity. For example, we showed that removal of microbes hindered transduction of vascular endothelial growth factor-dependent signals in the developing vasculature, resulting in impaired intestinal vascularization. Our work provides a high-resolution atlas of intestinal cellular composition in the developing fish gut and details the effects of the microbiome on each cell type.

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