Biology subjects

Psifidi, A.

Publications and source records attributed to Psifidi, A..

8 recordsLinked to original sources

bioRxiv2025

Interleukin 10 controls the balance between tolerance, pathogen elimination and immunopathology in birds.

Effective mucosal immunity in the intestine involves a fine balance between tolerance of the microbiome, recognition and elimination of pathogens, and inflammatory tissue injury. The anti-inflammatory cytokine IL10 regulates these processes in the intestines of mice and humans; the anti-inflammatory activity of IL10 is also conserved in birds. To determine the function of IL10 in avian mucosal immunity, we generated germ line modifications of the chicken IL10 locus to abolish or reduce IL10 expression. In vitro analysis of macrophage response to lipopolysaccharide confirmed the loss of IL10 protein expression, the lack of dosage compensation in heterozygotes, and prevention of autocrine inhibition of nitric oxide production in homozygous IL10 knockout macrophages. IL10-deficiency significantly altered the composition of the caecal microbiome, but unlike IL10-deficient mice and humans, IL10-deficient chickens did not exhibit spontaneous colitis. Following experimental challenge with Salmonella enterica serovar Typhimurium or Campylobacter jejuni in IL10-deficient chickens, enhanced clearance of the pathogens was associated with elevated transcription of pro-inflammatory genes and increased infiltration of inflammatory cells into gut mucosa. In IL10-deficient chickens challenged with the parasite Eimeria tenella, pathogen clearance was accelerated but caecal lesions were more severe and weight gain was compromised. Neither the heterozygous IL10 knockout nor a homozygous IL10 enhancer mutation had a major effect on pathogen clearance or inflammation in any of the challenge models. Our findings highlight the intrinsic compromise in mucosal immune response and have important implications for the development of strategies to combat avian and zoonotic pathogens in poultry.

immunology↗

bioRxiv2024

Impact of commercial gut health interventions on caecal metagenome and broiler performance

BackgroundMaintaining gut health is a persistent and unresolved challenge in the poultry industry. Given the critical role of gut health in chicken performance and welfare, there is a pressing need to identify effective gut health intervention (GHI) strategies to ensure optimal outcomes in poultry farming. In this study, across three broiler production cycles, we compared the metagenomes and performance of broilers provided with ionophores as control against birds subjected to five different GHI combinations involving vaccination, probiotics, prebiotics, essential oils, and reduction of ionophore use. ResultsUsing a binning strategy, 84 ([≥]75% completeness, [≤] 5% contamination) metagenome-assembled genomes (MAGs) from 118 caecal samples were recovered and annotated for their metabolic potential. The majority of these (n = 52, 61%) had a differential response across all cohorts and are associated with the performance parameter - European Poultry Efficiency Factor (EPEF). The control group exhibited the highest EPEF, followed closely by the cohort where probiotics are used in conjunction with vaccination. The use of Probiotics B, a commercial Bacillus strain-based formulation, was determined to contribute to the superior performance of birds. GHI supplementation generally affected abundance of microbial enzymes relating to carbohydrate and protein digestion, and metabolic pathways relating to energy, nucleotide synthesis, short-chain fatty acid synthesis, and drug-transport systems. These shifts are hypothesised to differentiate performance among groups and cycles, highlighting the beneficial role of several bacteria including Rikenella microfusus and UBA7160 species. ConclusionsAll GHIs are shown to be effective methods for gut microbial modulation, with varying influences on MAG diversity, composition and microbial functions. These metagenomic insights greatly enhance our understanding of microbiota-related metabolic pathways, enabling us to devise strategies against enteric pathogens related to poultry products and presenting new opportunities to improve overall poultry performance and health.

microbiology↗

bioRxiv2023

Identification of methylation markers for age and Bovine Respiratory Disease in dairy cattle

Methylation profiles of animals is known to differ by age and disease status. Bovine respiratory disease (BRD), a complex infectious disease, primarily affects calves and has significant impact on animal welfare and the cattle industry, predominantly from production losses. BRD susceptibility is multifactorial, influenced by both environmental and genetic factors. We investigated the epigenetic profile of BRD susceptibility in calves and age-related methylation differences between healthy calves and adult dairy cows using Reduced Representation Bisulfite Sequencing (RRBS). We identified 3,452 genes within differentially methylated regions between calves and adults. Functional analysis revealed enrichment of developmental pathways including cell fate commitment and tissue morphogenesis. Between healthy and BRD affected calves, 964 genes were identified within differentially methylated regions. Immune and vasculature regulatory pathways were enriched and key candidates in BRD susceptibility involved in complement cascade regulation, vasoconstriction and respiratory cilia structure and function were identified.

genetics↗

bioRxiv2021

Targeted next-generation sequencing of Candidate Regions Identified by GWAS Revealed SNPs Associated with IBD in GSDs

Canine Inflammatory bowel disease (IBD) is a chronic multifactorial disease, resulting from complex interactions between the intestinal immune system, microbiota and environmental factors in genetically predisposed dogs. Previously, we identified several single nucleotide polymorphisms (SNP) and regions on chromosomes (Chr) 7, 9, 11 and 13 associated with IBD in German shepherd dogs (GSD) using GWAS and FST association analyses. Here, building on our previous results, we performed a targeted next-generation sequencing (NGS) of a two Mb region on Chr 9 and 11 that included 14 of the newly identified candidate genes, in order to identify potential functional SNPs that could explain these association signals. Furthermore, correlations between genotype and treatment response were estimated. Results revealed several SNPs in the genes for canine EEF1A1, MDH2, IL3, IL4, IL13 and PDLIM, which, based on the known function of their corresponding proteins, further our insight into the pathogenesis of IBD in dogs. In addition, several pathways involved in innate and adaptive immunity and inflammatory responses (i.e. T helper cell differentiation, Th1 and Th2 activation pathway, communication between innate and adaptive immune cells and differential regulation of cytokine production in intestinal epithelial cells by IL-17A and IL-17F), were constructed involving the gene products in the candidate regions for IBD susceptibility. Interestingly, some of the identified SNPs were present in only one outcome group, suggesting that different genetic factors are involved in the pathogenesis of IBD in different treatment response groups. This also highlights potential genetic markers to predict the response in dogs treated for IBD.

genetics↗

bioRxiv2020

Life-long telomere attrition predicts health and lifespan in a large mammal

Telomere length measured in blood cells is predictive of subsequent adult health and survival across a range of vertebrate species. However, we currently do not know whether such associations result from among-individual differences in telomere length determined genetically or by environmental factors early in life, or from differences in the rate of telomere attrition over the course of life. Here, we measured relative leukocyte telomere length (RLTL) multiple times across the entire lifespan of dairy cattle in a research population that is closely monitored for health and milk production and where individuals are only culled in response to health issues and less due to poor milk production than on purely commercial farms. Our results clearly show that the average amount of telomere attrition over an individuals life, not their average or early life telomere length predicted when an individual was culled. Within-individual telomere length attrition could reflect environmental or physiological insults which may accumulate to predict individual health-span. We also show that animals with more telomere attrition in their first year of life were culled at a younger age, indicating that early life stressors may have a prolonged effect on adult life.

evolutionary biology↗

bioRxiv2020

Genetic control of Campylobacter colonisation in broiler chickens: genomic and transcriptomic characterisation

Campylobacter is the leading cause of bacterial foodborne gastroenteritis in many countries. Source attribution studies unequivocally identify the handling or consumption of contaminated poultry meat as the primary risk factor. One potential strategy to control Campylobacter is to select poultry with increased resistance to colonisation. We conducted genomic and transcriptomic analyses of commercial pedigree broilers exposed to Campylobacter to examine persistent colonisation of the caecum as a quantitative trait. 3,000 broilers were genotyped using a 50K single nucleotide polymorphism (SNP) array and imputed to 600K SNPs. Genotypes were analysed for associations with the number of viable Campylobacter in the caeca. Heritability of the trait was modest but significantly greater than zero (h2=0.11 {+/-} 0.03). Genome-wide association analyses confirmed quantitative trait loci (QTL) on chromosomes 14 and 16 previously identified using the progeny of crosses of inbred lines differing in resistance, and detected two additional genome-wide significant QTLs on chromosomes 19 and 26. RNA-Seq analysis of the transcriptome of caecal tonsils from birds at the low and high extremes of C. jejuni colonisation phenotype identified differentially transcribed genes, mainly located within the QTL on chromosome 16 and proximal to the major histocompatibility complex (MHC) locus. We also identified strong cis-QTLs located within the MHC suggesting the presence of cis-acting variation in both MHC class I, class II and BG genes. Multiple other cis-acting variants were identified in association with key immune genes (COPS3, CCL4, CR1L, C4BP, PLGR) in the other QTLs. Pathway and network analysis implicated cooperative functional pathways and networks in colonisation, including those related to antigen presentation, innate and adaptive immune responses, calcium, and renin-angiotensin signalling. While co-selection for enhanced resistance and other breeding goal traits is feasible, the frequency of resistance-associated alleles was high in the population studied and non-genetic factors significantly influence Campylobacter colonisation in poultry. Author summaryCampylobacter infection is estimated to cause 95 million illnesses in people worldwide each year. Human infections mostly involve gastroenteritis, but can have severe complications. The handling or consumption of contaminated poultry meat is a key risk factor for human campylobacteriosis. The bacteria reach high numbers in the intestines of chickens reared for meat (broilers) and are frequently found on carcasses after slaughter. Effective vaccines against Campylobacter are not yet available, and treatments to reduce carcass contamination (e.g. chlorination) are not acceptable in some markets. One alternative is to breed for chickens with improved resistance to Campylobacter colonisation. To test the feasibility of this option in commercial birds, we analysed the genetic make-up of 3,000 pedigree broilers and determined the number of Campylobacter in their gut. There were associations between specific regions of the chicken genome and resistance to Campylobacter. Within some of these regions, expression of certain genes differed between birds at the low and high extremes of Campylobacter colonisation, providing a potential explanation for genetic variation in resistance. Selection of poultry with increased resistance to Campylobacter colonisation may be a complementary strategy to improved biosecurity, management, handling and processing procedures to reduce the burden of Campylobacter on human health.

genomics↗

bioRxiv2019

Genomic analyses underpin the feasibility of concomitant genetic improvement of milk yield and mastitis resistance in dairy sheep

Milk yield is the most important dairy sheep trait and constitutes the key genetic improvement goal via selective breeding. Mastitis is one of the most prevalent diseases, significantly impacting on animal welfare, milk yield and quality, while incurring substantial costs. Our objectives were to determine the feasibility of a concomitant genetic improvement programme for enhanced milk production and resistance to mastitis. Individual records for milk yield and four mastitis-related traits were collected monthly throughout lactation for 609 ewes of the Chios breed. All ewes were genotyped with a mastitis specific custom-made 960 single nucleotide polymorphism array. We performed genomic association studies, (co)variance component estimation and pathway enrichment analysis, and characterised gene expression levels and the extent of allelic expression imbalance. Presence of heritable variation for milk yield was confirmed. There was no significant genetic correlation between milk yield and mastitis. Environmental factors appeared to favour both milk production and udder health. Four Quantitative Trait Loci (QTLs) affecting milk yield were detected on chromosomes 2, 12, 16 and 19, in locations distinct from those previously identified to affect mastitis resistance. Pathways, networks and functional gene clusters for milk yield were identified. Seven genes (DNAJA1, DNAJC10, FGF10, GHR, HMGCS1, LYPLA1, OXCT1) located within the QTL regions were highly expressed in both the mammary gland and milk transcriptome, suggesting involvement in milk synthesis and production. Furthermore, the expression of four genes (DNAJC10, FGF10, OXCT1, EMB) was enriched in immune tissues implying a favourable pleiotropic effect or likely role in milk production during udder infection. In conclusion, the absence of genetic antagonism between milk yield and mastitis resistance suggests that simultaneous genetic improvement of both traits be achievable. The detection of milk yield QTLs with the mastitis array underpins the latters utility as a breeding tool for the genetic enhancement of both traits.

genetics↗

bioRxiv2018

Combination of novel and public RNA-seq datasets to generate an mRNA expression atlas for the domestic chicken

BackgroundThe domestic chicken (Gallus gallus) is widely used as a model in developmental biology and is also an important livestock species. We describe a novel approach to data integration to generate an mRNA expression atlas for the chicken spanning major tissue types and developmental stages, using a diverse range of publicly-archived RNA-seq datasets and new data derived from immune cells and tissues.\n\nResultsRandomly down-sampling RNA-seq datasets to a common depth and quantifying expression against a reference transcriptome using the mRNA quantitation tool Kallisto ensured that disparate datasets explored comparable transcriptomic space. The network analysis tool Miru was used to extract clusters of co-expressed genes from the resulting expression atlas, many of which were tissue or cell-type restricted, contained transcription factors that have previously been implicated in their regulation, or were otherwise associated with biological processes, such as the cell cycle. The atlas provides a resource for the functional annotation of genes that currently have only a locus ID. We cross-referenced the RNA-seq atlas to a publicly available embryonic Cap Analysis of Gene Expression (CAGE) dataset to infer the developmental time course of organ systems, and to identify a signature of the expansion of tissue macrophage populations during development.\n\nConclusionExpression profiles obtained from public RNA-seq datasets - despite being generated by different laboratories using different methodologies - can be made comparable to each other. This meta-analytic approach to RNA-seq can be extended with new datasets from novel tissues, and is applicable to any species.

genomics↗