scholarly journals Dense time-course gene expression profiling of the Drosophila melanogaster innate immune response

2020 ◽  
Author(s):  
Florencia Schlamp ◽  
Sofie Y. N. Delbare ◽  
Angela M. Early ◽  
Martin T. Wells ◽  
Sumanta Basu ◽  
...  

ABSTRACTImmune responses need to be initiated rapidly, and maintained as needed, to prevent establishment and growth of infections. Still, immune genes differ in both initiation kinetics and shutdown dynamics. Here, we performed an RNA-seq time course on D. melanogaster with 20 time points post-LPS injection. A combination of methods, including spline fitting, cluster analysis, and Granger Causality inference, allowed detailed dissection of expression profiles and functional annotation of genes through guilt-by-association. We identified antimicrobial peptides as immediate-early response genes with a sustained up-regulation up to five days after stimulation, and genes in the IM family as having early and transient responses. We further observed a strong trade-off with metabolic genes, which strikingly recovered to pre-infection levels before the immune response was fully resolved. This high-dimensional dataset enables the comprehensive study of immune response dynamics through the parallel application of multiple temporal data analysis methods.

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Florencia Schlamp ◽  
Sofie Y. N. Delbare ◽  
Angela M. Early ◽  
Martin T. Wells ◽  
Sumanta Basu ◽  
...  

Abstract Background Immune responses need to be initiated rapidly, and maintained as needed, to prevent establishment and growth of infections. At the same time, resources need to be balanced with other physiological processes. On the level of transcription, studies have shown that this balancing act is reflected in tight control of the initiation kinetics and shutdown dynamics of specific immune genes. Results To investigate genome-wide expression dynamics and trade-offs after infection at a high temporal resolution, we performed an RNA-seq time course on D. melanogaster with 20 time points post Imd stimulation. A combination of methods, including spline fitting, cluster analysis, and Granger causality inference, allowed detailed dissection of expression profiles, lead-lag interactions, and functional annotation of genes through guilt-by-association. We identified Imd-responsive genes and co-expressed, less well characterized genes, with an immediate-early response and sustained up-regulation up to 5 days after stimulation. In contrast, stress response and Toll-responsive genes, among which were Bomanins, demonstrated early and transient responses. We further observed a strong trade-off with metabolic genes, which strikingly recovered to pre-infection levels before the immune response was fully resolved. Conclusions This high-dimensional dataset enabled the comprehensive study of immune response dynamics through the parallel application of multiple temporal data analysis methods. The well annotated data set should also serve as a useful resource for further investigation of the D. melanogaster innate immune response, and for the development of methods for analysis of a post-stress transcriptional response time-series at whole-genome scale.


2020 ◽  
Author(s):  
Florencia Schlamp ◽  
Sofie Delbare ◽  
Angela M. Early ◽  
Martin T. Wells ◽  
Sumanta Basu ◽  
...  

Abstract BackgroundImmune responses need to be initiated rapidly, and maintained as needed, to prevent establishment and growth of infections. At the same time, resources need to be balanced with other physiological processes. On the level of transcription, studies have shown that this balancing act is reflected in tight control of the initiation kinetics and shutdown dynamics of specific immune genes. ResultsTo investigate expression dynamics and trade-offs after infection genome-wide and with high temporal resolution, we performed an RNA-seq time course on D. melanogaster with 20 time points post-LPS injection. A combination of methods, including spline fitting, cluster analysis, and Granger Causality inference, allowed detailed dissection of expression profiles, lead-lag interactions, and functional annotation of genes through guilt-by-association. We identified genes encoding antimicrobial peptides and co-expressed, less well characterized genes, as immediate-early response genes with a sustained up-regulation up to five days after stimulation. In contrast, stress response genes and additional immune genes, among which were Bomanins, demonstrated early and transient responses. We further observed a strong trade-off with metabolic genes, which strikingly recovered to pre-infection levels before the immune response was fully resolved. ConclusionsThis high-dimensional dataset enabled the comprehensive study of immune response dynamics through the parallel application of multiple temporal data analysis methods. Multivariate Granger causality analysis proved to be a valuable addition to classical time course analysis methods such as clustering, due to its ability to define directed networks of lead-lag patterns.


2012 ◽  
Vol 25 (1) ◽  
pp. 107-118 ◽  
Author(s):  
Daniel Gonzalez-Ibeas ◽  
Joaquin Cañizares ◽  
Miguel A. Aranda

Resistance to Watermelon mosaic virus (WMV) in melon (Cucumis melo L.) accession TGR-1551 is characterized by a significant reduction in virus titer, and is inherited as a recessive, loss-of-susceptibility allele. We measured virus RNA accumulation in TGR-1551 plants and a susceptible control (‘Tendral’) by real-time quantitative polymerase chain reaction, and also profiled the expression of 17,443 unigenes represented on a melon microarray over a 15-day time course. The virus accumulated to higher levels in cotyledons of the resistant variety up to 9 days postinoculation (dpi) but, thereafter, levels increased in the susceptible variety while those in the resistant variety declined. Microarray experiments looking at the early response to infection (1 and 3 dpi), as well as responses after 7 and 15 dpi, revealed more profound transcriptomic changes in resistant plants than susceptible ones. The gene expression profiles revealed deep and extensive transcriptome remodeling in TGR-1551 plants, often involving genes with pathogen response functions. Overall, our data suggested that resistance to WMV in TGR-1551 melon plants is associated with a defense response, which contrasts with the recessive nature of the resistance trait.


2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Hao Zhou ◽  
Shun Chen ◽  
Mingshu Wang ◽  
Renyong Jia ◽  
Dekang Zhu ◽  
...  

Abstract Both Tembusu virus (TMUV) and goose parvovirus (GPV) are causative agents of goose disease. However, the host immune response of the goose against these two different categories of virus has not been well documented. Here, we compared the clinical symptoms and pathological characteristics, antigen distribution and intensity, and expression of immune-related genes in TMUV- and GPV- infected goose. The immunohistochemistry analysis demonstrated that GPV was primarily located in the liver, lung, small intestine, and rectum, while TMUV was situated in the liver, brain, spleen, and small intestine. The induction of IFNγ and proinflammatory cytokines is highly associated with the distribution profiles of antigen and CD8α+ molecules. The effector function of CD8 T cells may be accomplished by the secretion of IFNγ together with high expression of proinflammatory cytokines such as IL1 and IL6. Remarkably, significant increases in the transcription of immune genes were observed after infection, which suggested that both GPV and TMUV can effectively induce immune response in goose PMBCs. This study will provide fundamental information for goose molecular immunology in defending against pandemic viruses.


PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6359 ◽  
Author(s):  
Yu Zhang ◽  
Yang Chen ◽  
Tiantian Gu ◽  
Qi Xu ◽  
Guoqiang Zhu ◽  
...  

Persistent colonization of the avian reproductive tract by Salmonella enterica serovar Enteritidis (SE) negatively affects egg production and contaminates the egg. The immune function of the ovary and oviduct is essential for protection from infection and for the production of wholesome eggs. However, the immune response of laying ducks during SE infection is not well-understood. In this study, ducks (Anas platyrhynchos) were infected with SE and were systematically monitored for fecal shedding during a 13-week period. We also assessed bacterial distribution in the reproductive tract and classified infected ducks as resistant or susceptible based on the presence of tissue lesions and on SE isolation from fecal samples. We found that infected animals had persistent, but intermittent, bacterial shedding that resulted in the induction of carrier ducks. Laying rate and egg quality were also decreased after SE infection (P < 0.05). SE readily colonized the stroma, small follicle, isthmus, and vagina in the reproductive tracts of susceptible ducks. Immunoglobulin (IgA, IgG, IgM) levels were higher in susceptible ducks compared with resistant birds (P < 0.05); T-lymphocyte subpopulations (CD3+, CD4+, CD8+) displayed the opposite trend. qRT-PCR analysis was used to examine expression profiles of immune response genes in the reproductive tract of infected ducks. The analysis revealed that immune genes, including toll-like receptors (TLR2, TLR4-5, TLR15, TLR21), NOD-like receptors (NOD1, NLRX1, NLRP12), avian β-defensins (AvβD4-5, AvβD7, AvβD12), cytokines (IL-6, IL-1β, IFN-γ), and MyD88 were markedly upregulated in the reproductive tracts of SE-infected ducks (all P < 0.05); TLR3, TLR7, NLRC3, NLRC5, and TNF-α were significantly downregulated. These results revealed that SE infection promoted lower egg production and quality, and altered the expression of TLRs, NLRs, AvβDs, and cytokine family genes. These findings provide a basis for further investigation of the physiological and immune mechanisms of SE infection in laying ducks.


Author(s):  
P. Sivasankar ◽  
K. Riji John ◽  
M. Rosalind George ◽  
M. Mohamed Mansoor ◽  
P. Magesh Kumar ◽  
...  

Background: Control of viral disease outbreaks in aquaculture and minimizing the loss of production can be achieved by development of effective vaccines. Efficacy of these vaccines can be improved by using adjuvants, immunostimulants or vaccine carriers. In this study, inactivated similar damselfish virus (SRDV) vaccine was prepared and expression profiles of immune related genes against virus challenge of the vaccine were investigated in seabass (Lates calcarifer). Methods: Formalin-inactivated virus vaccine was developed to assess its immune responses to SRDV challenge in fish. The immune response was induced by intra-peritoneal injection with inactivated viral vaccine added Quil-A® adjuvant. The transcriptional levels of immune genes IRF-7 and IL-10 were evaluated in the spleen and kidney of seabass from different groups by quantitative real-time RT-PCR assays. Result: Expression profiles of both genes (IRF-7 and IL-10) in the kidney and spleen of seabass immunized with vaccine added adjuvant were up-regulated at 48 hpi of the virus. In comparison, spleen of seabass immunized with vaccine added adjuvant showed highest expression profiles than kidney. The current study provides evidence for the presence of expression profiles of immune-related genes during the SRDV infection. The study also strongly suggests that Quil-A® adjuvant enhances the immune response of the vaccine candidates.


2021 ◽  
Vol 14 (1) ◽  
pp. 41
Author(s):  
Hana Votavova ◽  
Zuzana Urbanova ◽  
David Kundrat ◽  
Michaela Dostalova Merkerova ◽  
Martin Vostry ◽  
...  

Deferasirox (DFX) is an oral iron chelator used to reduce iron overload (IO) caused by frequent blood cell transfusions in anemic myelodysplastic syndrome (MDS) patients. To study the molecular mechanisms by which DFX improves outcome in MDS, we analyzed the global gene expression in untreated MDS patients and those who were given DFX treatment. The gene expression profiles of bone marrow CD34+ cells were assessed by whole-genome microarrays. Initially, differentially expressed genes (DEGs) were determined between patients with normal ferritin levels and those with IO to address the effect of excessive iron on cellular pathways. These DEGs were annotated to Gene Ontology terms associated with cell cycle, apoptosis, adaptive immune response and protein folding and were enriched in cancer-related pathways. The deregulation of multiple cancer pathways in iron-overloaded patients suggests that IO is a cofactor favoring the progression of MDS. The DEGs between patients with IO and those treated with DFX were involved predominantly in biological processes related to the immune response and inflammation. These data indicate DFX modulates the immune response mainly via neutrophil-related genes. Suppression of negative regulators of blood cell differentiation essential for cell maturation and upregulation of heme metabolism observed in DFX-treated patients may contribute to the hematopoietic improvement.


2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Jan K. Nowak ◽  
Marzena Dworacka ◽  
Nazgul Gubaj ◽  
Arystan Dossimov ◽  
Zhumabek Dossimov ◽  
...  

Abstract Background The expression profiles of the intestinal mucosa have not been comprehensively investigated in asthma. We aimed to explore this in the Correlated Expression and Disease Association Research (CEDAR) patient cohort. Methods Differential expression analysis of ileal, transverse colon, and rectal biopsies were supplemented by a comparison of transcriptomes from platelets and leukocytes subsets, including CD4+, CD8+, CD14+, CD15+, and CD19+ cells. Asthma patients (n = 15) and controls (n = 15) had similar age (p = 0.967), body mass index (p = 0.870), similar numbers of females (80%) and smoking rates (13.3%). Results Significant differential expression was found in the ileum alone, and not in any other cell/tissue types. More genes were found to be overexpressed (1,150) than under-expressed (380). The most overexpressed genes included Fc Fragment of IgG Binding Protein (FCGBP, logFC = 3.01, pFDR = 0.015), Mucin 2 (MUC2, logFC = 2.78, pFDR = 0.015), and Alpha 1B Defensin (DEFA1B, logFC = 2.73, pFDR = 0.024). Gene ontology implicated the immune system, including interleukins 4 and 13, as well as antimicrobial peptides in this overexpression. There was concordance of gene over- (STAT1, XBP1) and underexpression (NELF, RARA) in asthma and Crohn’s disease ileum when our results were compared to another dataset (p = 3.66 × 10–7). Conclusion Ileal mucosa in asthma exhibits a specific transcriptomic profile, which includes the overexpression of innate immune genes, mostly characteristic of Paneth and goblet cells, in addition to other changes that may resemble Crohn’s disease.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Arika Fukushima ◽  
Masahiro Sugimoto ◽  
Satoru Hiwa ◽  
Tomoyuki Hiroyasu

Abstract Background Historical and updated information provided by time-course data collected during an entire treatment period proves to be more useful than information provided by single-point data. Accurate predictions made using time-course data on multiple biomarkers that indicate a patient’s response to therapy contribute positively to the decision-making process associated with designing effective treatment programs for various diseases. Therefore, the development of prediction methods incorporating time-course data on multiple markers is necessary. Results We proposed new methods that may be used for prediction and gene selection via time-course gene expression profiles. Our prediction method consolidated multiple probabilities calculated using gene expression profiles collected over a series of time points to predict therapy response. Using two data sets collected from patients with hepatitis C virus (HCV) infection and multiple sclerosis (MS), we performed numerical experiments that predicted response to therapy and evaluated their accuracies. Our methods were more accurate than conventional methods and successfully selected genes, the functions of which were associated with the pathology of HCV infection and MS. Conclusions The proposed method accurately predicted response to therapy using data at multiple time points. It showed higher accuracies at early time points compared to those of conventional methods. Furthermore, this method successfully selected genes that were directly associated with diseases.


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