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Transcriptome-wide analysis reveals different categories of response to a standardised immune challenge in a wild rodent.

ABSTRACT: Individuals vary in their immune response and, as a result, some are more susceptible to infectious disease than others. Little is known about the nature of this individual variation in natural populations, or which components of immune pathways are most responsible, but defining this underlying landscape of variation is an essential first step to understanding the drivers of this variation and, ultimately, predicting the outcome of infection. We describe transcriptome-wide variation in response to a standardised immune challenge in wild field voles. We find that genes (hereafter 'markers') can be categorised into a limited number of types. For the majority of markers, the response of an individual is dependent on its baseline expression level, with significant enrichment in this category for conventional immune pathways. Another, moderately sized, category contains markers for which the responses of different individuals are also variable but independent of their baseline expression levels. This category lacks any enrichment for conventional immune pathways. We further identify markers which display particularly high individual variability in response, and could be used as markers of immune response in larger studies. Our work shows how a standardised challenge performed on a natural population can reveal the patterns of natural variation in immune response.

SUBMITTER: Wanelik KM

PROVIDER: S-EPMC7198573 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Transcriptome-wide analysis reveals different categories of response to a standardised immune challenge in a wild rodent.

Wanelik Klara M KM Begon Mike M Arriero Elena E Bradley Janette E JE Friberg Ida M IM Jackson Joseph A JA Taylor Christopher H CH Paterson Steve S

Scientific reports 20200504 1

Individuals vary in their immune response and, as a result, some are more susceptible to infectious disease than others. Little is known about the nature of this individual variation in natural populations, or which components of immune pathways are most responsible, but defining this underlying landscape of variation is an essential first step to understanding the drivers of this variation and, ultimately, predicting the outcome of infection. We describe transcriptome-wide variation in response ...[more]

PMID: 32366957

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Project description:IntroductionThere are difficulties in creating direct antiviral drugs for all viruses, including new, suddenly arising infections, such as COVID-19. Therefore, pathogenesis-directed therapy is often necessary to treat severe viral infections and comorbidities associated with them. Despite significant differences in the etiopathogenesis of viral diseases, in general, they are associated with significant dysfunction of the immune system. Study of common mechanisms of immune dysfunction caused by different viral infections can help develop novel therapeutic strategies to combat infections and associated comorbidities.MethodsTo identify common mechanisms of immune functions disruption during infection by nine different viruses (cytomegalovirus, Ebstein-Barr virus, human T-cell leukemia virus type 1, Hepatitis B and C viruses, human immunodeficiency virus, Dengue virus, SARS-CoV, and SARS-CoV-2), we analyzed the corresponding transcription profiles from peripheral blood mononuclear cells (PBMC) using the originally developed pipeline that include transcriptome data collection, processing, normalization, analysis and search for master regulators of several viral infections. The ten datasets containing transcription data from patients infected by nine viruses and healthy people were obtained from Gene Expression Omnibus. The analysis of the data was performed by Genome Enhancer pipeline.ResultsWe revealed common pathways, cellular processes, and master regulators for studied viral infections. We found that all nine viral infections cause immune activation, exhaustion, cell proliferation disruption, and increased susceptibility to apoptosis. Using network analysis, we identified PBMC receptors, representing proteins at the top of signaling pathways that may be responsible for the observed transcriptional changes and maintain the current functional state of cells.DiscussionThe identified relationships between some of them and virus-induced alteration of immune functions are new and have not been found earlier, e.g., receptors for autocrine motility factor, insulin, prolactin, angiotensin II, and immunoglobulin epsilon. Modulation of the identified receptors can be investigated as one of therapeutic strategies for the treatment of severe viral infections.

Project description:Depression symptoms following immune response to a challenge have been reported after the recovery from sickness. A RNA-Seq study of the dysregulation of the microglia transcriptome in a model of inflammation-associated depressive behavior was undertaken. The transcriptome of microglia from mice at day 7 after Bacille Calmette Guérin (BCG) challenge was compared to that from unchallenged Control mice and to the transcriptome from peripheral macrophages from the same mice. Among the 562 and 3,851 genes differentially expressed between BCG-challenged and Control mice in microglia and macrophages respectively, 353 genes overlapped between these cells types. Among the most differentially expressed genes in the microglia, serum amyloid A3 (Saa3) and cell adhesion molecule 3 (Cadm3) were over-expressed and coiled-coil domain containing 162 (Ccdc162) and titin-cap (Tcap) were under-expressed in BCG-challenged relative to Control. Many of the differentially expressed genes between BCG-challenged and Control mice were associated with neurological disorders encompassing depression symptoms. Across cell types, S100 calcium binding protein A9 (S100A9), interleukin 1 beta (Il1b) and kynurenine 3-monooxygenase (Kmo) were differentially expressed between challenged and control mice. Immune response, chemotaxis, and chemokine activity were among the functional categories enriched by the differentially expressed genes. Functional categories enriched among the 9,117 genes differentially expressed between cell types included leukocyte regulation and activation, chemokine and cytokine activities, MAP kinase activity, and apoptosis. More than 200 genes exhibited alternative splicing events between cell types including WNK lysine deficient protein kinase 1 (Wnk1) and microtubule-actin crosslinking factor 1(Macf1). Network visualization revealed the capability of microglia to exhibit transcriptome dysregulation in response to immune challenge still after resolution of sickness symptoms, albeit lower than that observed in macrophages. The persistent transcriptome dysregulation in the microglia shared patterns with neurological disorders indicating that the associated persistent depressive symptoms share a common transcriptome basis.

Project description:Although a number of nongenetic factors have been reported to be able to modulate skeletal muscle phenotypes in meat-type birds, neither the underlying mechanisms nor the muscle group-specific phenotypic and molecular responses have been fully understood. In the present study, a total of 240 broiler ducks were used to compare the effects of floor raising system (FRS) and net raising system (NRS) on the physicochemical properties and global gene expression profiles of both breast and thigh muscles at the posthatching week 4 (W4), W8, and W13. Our results showed that compared with FRS, NRS generally induced higher pH, lower lightness (L∗) and yellowness (b∗), lower drip loss and cooking loss, and lower shear force in either breast or thigh muscles during early posthatching stages but subsequently showed less pronounced or even reverse effects. Meanwhile, it was observed that the raising system differently changed the myofiber characteristics depending on the muscle group and the developmental stage. Genome-wide transcriptome analysis showed that compared with FRS, NRS induced the most extensive gene expression changes in breast muscle (BM) at W4 but in thigh muscle (TM) at W13, suggesting the asynchronous molecular responses of BM and TM to the raising system and period. Most of differentially expressed genes in either BM or TM between NRS and FRS were enriched in the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes terms associated with regulation of muscle cellular functions, metabolic and contractile activities, and tissue remodeling, indicating similar molecular mechanisms principally responsible for the raising system-caused phenotypic changes in both muscle groups. Nevertheless, several crucial pathways (e.g., adipocytokine signaling, AGE-RAGE signaling, and apoptosis) and genes (e.g., ANO6, ACER2, UCP3, DTL, and TMEM120A) were tightly related to the muscle group-specific adaptive remodeling on different raising systems. These data could not only contribute to a better understanding of the molecular mechanisms behind meat quality but also provide novel insights into the molecular causes of the muscle group-specific adaptive remodeling in response to environmental stimuli.

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Transcriptome-wide analysis reveals different categories of response to a standardised immune challenge in a wild rodent.

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Transcriptome-wide analysis reveals different categories of response to a standardised immune challenge in a wild rodent.

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