Biology subjects

Dubois, E.

Publications and source records attributed to Dubois, E..

7 recordsLinked to original sources

bioRxiv2024

Co-infection with two iflaviruses (deformed wing virus and sacbrood virus) affects viral and immune dynamics and synergistically increases honey bee mortality

The honey bee microbiome includes a wide variety of viruses. While most of them usually remain commensal, some can become pathogenic in specific contexts. Of these, one is that of deformed wing virus (DWV) and another, sacbrood virus (SBV). Although co-infection is the norm rather than the exception, most of the time these viruses have been studied independently. When investigated as co-infections, past studies have focused on their effects on the honey bee brood. In this study, we co-inoculated adult honey bees at emergence with DWV by injection and SBV orally (acting as the viral transmission by Varroa destructor and by trophallaxis or food, respectively), either simultaneously or sequentially. Using optical counters, we were able to track the survival and behaviour of these honey bees within colonies. Through regular in-hive sampling, we monitored the evolution of their viral loads as well as the expression of eight immune genes involved in honey bee anti-viral immunity. Here, we show that co-inoculations of DWV and SBV synergistically increase the virulence of DWV and conditionally promote the replication of both viruses. Finally, our results show that immune responses in adult honey bees depend on DWV genotypes and whether replication originates from a superinfecting virus or a virus already present in bees. Author SummaryHoney bees are highly social pollinators that live in crowded colonies. Their population density and the high frequency of interactions between individuals favours disease transmission and makes colonies susceptible to pathogen outbreaks. Many viruses commonly infect honey bees, however, they are often studied as single infections. As an effort to better understand interactions between honey bees and multiple viral populations, we co-inoculated young bees with two common honey bee viruses (deformed wing virus and sacbrood virus), released them in colonies and monitored their health and behaviour. Our findings show evidence of synergies between both viruses, as we show that a virus seemingly harmless for adult bees (sacbrood virus) may actually increase the virulence of another virus (deformed wing virus). These results highlight the importance of monitoring and studying multiple pathogens at once for a better understanding of the threat they represent to colony health and survival.

pathology↗

bioRxiv2023

Alteration of mechanical stresses in the murine brain by age and hemorrhagic stroke

Residual mechanical stresses in tissues arise during rapid differential growth or remodeling such as in morphogenesis and cancer. These residual stresses, also known as solid stresses, are distinct from fluid pressures and dissipate in most healthy adult organs as the rate of growth decreases. However, studies have shown that residual stresses remain substantially high even in mature, healthy brains. The genesis and consequences of these mechanical stresses in a healthy brain, and in aging and disease remain to be explored. Here, we utilized and validated our previously developed method to map residual mechanical stresses in the brains of mice in three different age groups: 5-7 days, 8-12 weeks, and 22 months old. We found that residual solid stress increases rapidly from 5-7 days to 8-12 weeks in mice, and remains high even in mature 22-month-old mice brains. Three-dimensional mapping of the residual stresses revealed an increasing trend from anterior to posterior in coronal sections of the brain. Since the brain is rich in negatively charged hyaluronic acid, we evaluated the contribution of charged extracellular matrix (ECM) constituents in maintaining solid stress levels. We found that lower ionic strength leads to elevated solid stresses, a finding consistent with the unshielding effect of low ionic strength and the subsequent expansion of charged ECM components. Lastly, we demonstrated that hemorrhagic stroke, accompanied by loss of cellular density, resulted in decreased levels of residual stress in the murine brain. Our findings contribute to a better understanding of the spatiotemporal alteration of residual solid stresses in healthy and diseased brains, a crucial step toward uncovering the biological and immunological consequences of this understudied mechanical phenotype in the brain. Significance StatementWhile emerging evidence highlights the importance of solid stresses in embryogenesis and tumor growth, the genesis and consequences of residual solid stresses in the adult normal brain remain poorly understood. Understanding the spatiotemporal distribution and alteration of the residual solid stresses as the brain ages and is impacted by neuropathologies, such as a stroke, will elucidate the biological and immunological consequences of maintaining these stresses. This study suggests solid stress could serve as a potential biomarker in aging and diseases associated to the brain.

biophysics↗

bioRxiv2022

Whole blood transcriptome profiles of trypanotolerant and trypanosusceptible cattle highlight a differential modulation of metabolism and immune response during infection by Trypanosoma congolense

Animal African trypanosomosis, caused by blood protozoan parasites transmitted mainly by tsetse flies, represents a major constraint for millions of cattle in sub-Saharan Africa. Exposed cattle include trypanosusceptible indicine breeds, severely affected by the disease, and West African taurine breeds called trypanotolerant owing to their ability to control parasite development, survive and grow in enzootic areas. Until now the genetic basis of trypanotolerance remains unclear. Here, to improve knowledge of the biological processes involved in trypanotolerance versus trypanosusceptibility, we identified bovine genes differentially expressed in five West African cattle breeds during an experimental infection by Trypanosoma congolense and their biological functions. To this end, whole blood genome-wide transcriptome of three trypanotolerant taurine breeds (NDama, Lagune and Baoule), one susceptible zebu (Zebu Fulani) and one African taurine x zebu admixed breed (Borgou) were profiled by RNA sequencing at four time points, one before and three during infection. As expected, infection had a major impact on cattle blood transcriptome regardless of the breed. The functional analysis of differentially expressed genes over time in each breed confirmed an early activation of the innate immune response, followed by an activation of the humoral response and an inhibition of T cell functions at the chronic stage of infection. More importantly, we highlighted overlooked features, such as a strong disturbance in host metabolism and cellular energy production that differentiates trypanotolerant and trypanosusceptible breeds. NDama breed showed the earliest regulation of immune response, associated with a strong activation of cellular energy production, also observed in Lagune, and to a lesser extent in Baoule. Susceptible Zebu Fulani breed differed from other breeds by the strongest modification in lipid metabolism regulation. Overall, this study provides a better understanding of the biological mechanisms at work during infection, especially concerning the interplay between immunity and metabolism that seems differentially regulated depending on the cattle breeds.

pathology↗

bioRxiv2021

SMAD4 governs a feedforward regulation of the TGF-beta effects in CD8 T cells that contributes to preventing chronic intestinal inflammation

SMAD4, a key mediator of TGF-{beta} signaling, plays a crucial role in T cells to prevent chronic gut inflammation. However, the molecular mechanisms underlying this control remain elusive. Using different genetic and epigenetic approaches, we unexpectedly reveal that SMAD4 in CD8 T cells prevents chronic intestinal inflammation by a feedforward mechanism that is TGF-{beta}-independent. Prior to any TGF-{beta}-receptor engagement, SMAD4 acts as an active and basal repressor of epigenetic, transcriptional and functional TGF-{beta} imprinting in CD8 T cells. Thus, in sharp opposition to total TGF-{beta} signaling deletion, SMAD4 deletion impairs naive CD8 T cell effector predisposition but promotes CD8 T cell accumulation and epithelial retention by promoting their response to IL-7 and their expression of integrins such as Itgae. Besides, SMAD4 deletion unleashes the induction of a wide range of TGF-{beta}-signaling-repressors such as Smad7, Ski, Skil, and Smurf2 and hampers TGF-{beta}-mediated CD8 T cell immunosuppression. Mechanistically, prior to any TGF-{beta} signal, SMAD4 binds to the loci of several TGF-{beta}-target genes, and by regulating histone acetylation, represses their expression. The massive gut epithelial colonization, associated with their escape from the immunoregulatory TGF-{beta} effects overtakes their poor effector preconditioning and elicits microbiota-driven chronic epithelial CD8 T cell activation. Hence, in an anticipatory manner, independently of TGF-{beta}, SMAD4 governs a feedforward regulation of TGF-{beta} effects in CD8 T cells, preventing chronic intestinal inflammation.

immunology↗

bioRxiv2020

TALC: Transcription-Aware Long Read Correction

MotivationLong-read sequencing technologies are invaluable for determining complex RNA transcript architectures but are error-prone. Numerous "hybrid correction" algorithms have been developed for genomic data that correct long reads by exploiting the accuracy and depth of short reads sequenced from the same sample. These algorithms are not suited for correcting more complex transcriptome sequencing data. ResultsWe have created a novel reference-free algorithm called TALC (Transcription Aware Long Read Correction) which models changes in RNA expression and isoform representation in a weighted De-Bruijn graph to correct long reads from transcriptome studies. We show that transcription aware correction by TALC improves the accuracy of the whole spectrum of downstream RNA-seq applications and is thus necessary for transcriptome analyses that use long read technology. Availability and ImplementationTALC is implemented in C++ and available at https://gitlab.igh.cnrs.fr/lbroseus/TALC. Contactwilliam.ritchie@igh.cnrs.fr

bioinformatics↗

bioRxiv2018

Transcriptomic analyses with the progress of symbiosis in ‘crack-entry’ legume Arachis hypogaea highlight its contrast with ‘Infection thread’ adapted legumes

In root-nodule symbiosis, rhizobial invasion and nodule organogenesis is host controlled. In most legumes, rhizobia enter through infection-threads and nodule primordium in the cortex is induced from a distance. But in dalbergoid legumes like Arachis hypogaea, rhizobia directly invade cortical cells through epidermal cracks to generate the primordia. Herein we report the transcriptional dynamics with the progress of symbiosis in A. hypogaea at 1dpi: invasion; 4dpi: nodule primordia; 8dpi: spread of infection in nodule-like structure; 12dpi: immature nodules containing rod-shaped rhizobia; and 21dpi: mature nodules with spherical symbiosomes. Expression of putative orthologue of symbiotic genes in crack-entry legume A. hypogaea was compared with infection thread adapted model legumes. The contrasting features were (i) higher expression of receptors like LYR3, EPR3 as compared to canonical NFRs (ii) late induction of transcription factors like NIN, NSP2 and constitutive high expression of ERF1, EIN2, bHLH476 and (iii) induction of divergent pathogenesis responsive PR-1 genes. Additionally, symbiotic orthologues of SymCRK, FLOT4, ROP6, RR9, NOOT and SEN1 were not detectable and microsynteny analysis indicated the absence of RPG and DNF2 homologues in diploid parental genomes of A. hypogaea. The implications are discussed and a molecular framework that guide crack-entry symbiosis in A. hypogaea is proposed.

plant biology↗

bioRxiv2017

Transcription-dependent spreading of canonical yeast GATA factor across the body of highly expressed genes

GATA transcription factors are highly conserved among eukaryotes and play roles in transcription of genes implicated in cancer progression and hematopoiesis. However, although their consensus binding sites have been well defined in vitro, the in vivo selectivity for recognition by GATA factors remains poorly characterized. Using ChIP-Seq, we identified the Dal80 GATA factor targets in yeast. Our data reveal Dal80 binding to a large set of promoters, sometimes independently of GATA sites. Strikingly, Dal80 was also detected across the body of promoter-bound genes, correlating with high, Dal80-sensitive expression. Mechanistic single-gene experiments showed that Dal80 spreading across gene bodies is independent of intragenic GATA sites but requires transcription elongation. Consistently, Dal80 co-purified with the post-initiation form of RNA Polymerase II. Our work suggests that GATA factors could play dual, synergistic roles during transcription initiation and post-initiation steps, promoting efficient remodeling of the gene expression program in response to environmental changes.\n\nAuthor SummaryGATA transcription factors are highly conserved among eukaryotes and play key roles in cancer progression and hematopoiesis. In budding yeast, four GATA transcription factors are involved in the response to the quality of nitrogen supply. We have determined the whole genome binding profile of one of them, Dal80, and revealed that it also binds across the body or promoter-bound genes. Our observation that ORF binding correlated with elevated transcription levels and exquisite Dal80 sensitivity suggests that GATA factors could play other, unexpected roles at post-initiation stages in eukaryotes.

genomics↗