Biology subjects

Ballantyne, M.

Publications and source records attributed to Ballantyne, M..

5 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

Differential Ubiquitination of Host Proteins in Response to IPNV and ISAV viruses in Atlantic salmon

Viral diseases remain a major barrier to the sustainable production of farmed fish, primarily attributable to the absence of effective prevention and treatment options. Understanding host-pathogen interactions can guide the development of vaccines, antiviral therapies, or gene editing strategies. Ubiquitination is a key cell signalling molecule, known to regulate many aspects of immune functions but currently understudied in fish. This study leverages ubiquitin-enriched mass spectroscopy complemented with RNA sequencing to characterize the role of ubiquitination in response to infection. A challenge experiment was conducted by infecting Atlantic salmon head kidney (SHK-1) cells with Infectious salmon anaemia virus (ISAV) and Infectious pancreatic necrosis virus (IPNV). At 24- and 48 hours post-infection dramatic changes were observed in the global ubiquitination state of host proteins. Many post-translational modifying proteins increased in abundance upon ISAV infection, whilst IPNV infection resulted in a reduction in abundance of many of these proteins. Transcriptomics showed a delay in the activation of the antiviral response to ISAV infection, with major upregulation of genes associated with immune pathways only at 48h. On the contrary, IPNV infection resulted in upregulation of classic innate immune response genes at both timepoints. Clear activation of Rig-like receptor pathways is demonstrated in both infections, in addition to upregulation of both conserved and novel antiviral TRIM E3 ubiquitin ligate genes. Network analysis identified clusters of immune genes and putatively regulatory proteins showing differential ubiquitination upon viral infection. This study highlights the importance of post-translational control of the host innate immune response to viruses in Atlantic salmon. Clear differences in ubiquitination between two viruses indicate either virus-specific post-translational regulation or viral antagonism of the immune response. Additionally, the ubiquitination of various proteins was linked to the regulation of innate immune pathways, suggesting a direct role of ubiquitination in the regulation of antiviral responses. AUTHOR SUMMARYUbiquitination is a main cellular regulatory mechanism in all animal species, controlling the activity of many proteins within the cell. The role of ubiquitination in the regulation of immunity is well-established, and several direct interactions with viruses have been described, either as part of a strategy of the host to fight the infection or as a viral mechanism to evade the host immune response. In aquaculture, viral diseases currently represent the most important threat to the sustainability of the industry. However, very little is known about the interplay between ubiquitination and viral pathogens in fish species. In our study, we have assessed the ubiquitination response of Atlantic salmon to two production-relevant viruses, Infectious salmon anaemia virus (ISAV) and Infectious pancreatic necrosis virus (IPNV). We found remarkable differences in the ubiquitination profiles between the two infections, suggesting a key role of ubiquitination on the early immune response. We also discovered an association between the ubiquitination of certain regulatory proteins and the activation of antiviral pathways. This information could help develop new strategies to tackle viral diseases in aquaculture, such as the development of more effective vaccines or antiviral therapies, or inform gene editing efforts to generate disease resistant fish.

molecular biology↗

bioRxiv2024

A male-essential microRNA is key for avian sex chromosome dosage compensation

Birds have a sex chromosome system in which females are heterogametic (ZW) and males are homogametic (ZZ). The differentiation of avian sex chromosomes from ancestral autosomes entailed the loss of most genes from the W chromosome during evolution. However, to what extent mechanisms evolved that counterbalance the consequences of this extensive gene dosage reduction in female birds has remained unclear. Here we report functional in vivo and evolutionary analyses of a Z-chromosome-linked microRNA (miR-2954) with strongly male-biased expression that was previously proposed to play a key role in sex chromosome dosage compensation1. We knocked out miR-2954 in chicken, which resulted in early embryonic lethality of homozygous knockout males, likely due to the highly specific upregulation of dosage-sensitive Z-linked target genes of miR-2954. Our evolutionary gene expression analyses further revealed that these dosage-sensitive target genes have become upregulated on the single Z in female birds during evolution. Altogether, our work unveils a scenario where evolutionary pressures on females following W gene loss led to the evolution of transcriptional upregulation of dosage-sensitive genes on the Z not only in female but also in male birds. The resulting overabundance of transcripts in males resulting from the combined activity of two dosage-sensitive Z gene copies was in turn offset by the emergence of a highly targeted miR-2954-mediated transcript degradation mechanism during avian evolution. Our findings demonstrate that birds have evolved a unique sex chromosome dosage compensation system in which a microRNA has become essential for male survival.

evolutionary biology↗

bioRxiv2024

Characterisation of mesenchymal stromal cells in the skin of Atlantic salmon

BackgroundThe skin serves as the first line of defence for an organism against the external environment. Despite the global significance of salmon in aquaculture, a critical component of this first line of defence, mesenchymal stromal cells, remains unexplored. These pluripotent cells can differentiate into various tissues, including bone, cartilage, tendon, ligament, adipocytes, dermis, muscle and connective tissue within the skin. These cells are pivotal for preserving the integrity of skin tissue throughout an organisms lifespan and actively participate in wound healing processes. ResultsIn this study, we characterise mesenchymal stromal cells in detail for the first time in healthy Atlantic salmon tissue and during the wound healing process. Single-nucleus sequencing and spatial transcriptomics revealed the transcriptional dynamics of these cells, elucidating the differentiation pathways leading to osteogenic and fibroblast lineages in the skin of Atlantic salmon. We charted their activity during an in vivo wound healing time course, showing clear evidence of their active role during this process, as they become transcriptionally more active during the remodelling stage of wound healing. ConclusionsFor the first time, we chart the activity of sub-clusters of differentiating stromal cells during the process of wound healing, revealing different spatial niches of the various MSC subclusters, and setting the stage for investigations into the manipulation of MSCs to improve fish health.

genomics↗

bioRxiv2020

Single generation allele introgression into pure chicken breeds using Sire Dam Surrogate (SDS) mating

Poultry is the most abundant livestock species with over 60 billion chickens raised globally per year. While most chicken are produced from highly selected commercial flocks the many indigenous chicken breeds, which have low productivity and have not been highly selected, play an important role in rural economies across the world as they are well adapted to local environmental and scavenging conditions. The ability to rapidly transfer genetic changes between breeds of chicken will permit the transfer of beneficial alleles between poultry breeds as well as allow validation of genetic variants responsible for different phenotypic traits. Here, we generate a novel inducibly sterile surrogate host chicken. Introducing donor genome edited primordial cells into the sterile male and female host embryos produces chicken carrying only exogenous germ cells. Subsequent direct mating of the surrogate hosts, Sire Dam Surrogate (SDS) mating, recreates pure chicken breeds carrying the edited allele in heterozygous or homozygous states. We demonstrate the transfer and validation of two feather trait alleles, Dominant white and Frizzle traits into two pure chicken breeds using the SDS surrogate hosts. This technology will allow the rapid reconstitution of chicken breeds carrying desired genetic changes to investigate climate adaptation and disease resilience traits.

genetics↗