bioRxiv ScienceSearch

bioRxiv · 10.1101/2020.07.29.226894

Tolerance of liver fluke infection varies between breeds and producers in Scottish beef cattle

Abstract

Liver fluke (Fasciola spp.) are important helminth parasites of livestock globally and cause significant reductions in health and productivity of beef cattle. Attempts to control fluke have been thwarted by the difficulty of vaccine design, the evolution of flukicide resistance, and the need to control the intermediate snail host. Mechanisms to reduce the impact of parasites on animal performance have typically focused on promoting host resistance - defined as the ability of the host to kill and remove the parasite from its system - and such strategies include improving protein nutrition or selectively breeding for resistance. Organisms, however, have another broad mechanism for mitigating the impact of parasites: they can show tolerance, defined as the ability to maintain health or performance under increasing parasite burden. Tolerance has been studied in the plant literature for over a century, but there are very few empirical studies of parasite tolerance in livestock. In this study, we used data collected from >90,000 beef cattle to estimate the impact of the severity of liver fluke infection on performance and variation in tolerance of fluke. Severity of liver fluke infection was estimated using liver "fibrosis score" on a scale of 0-3 and performance estimated as (1) age at slaughter and (2) daily dead weight gain. Animals with higher fibrosis scores were slaughtered around two weeks later than animals with no fluke, and gained around 10g less weight per day. There was also considerable variation in these effects of fibrosis score, such that animals from different producers and breeds varied in their tolerance of fluke infection. While breeds did not vary in the association between fibrosis and age at slaughter, there was considerable variation among producers: high fibrosis score delayed slaughter by up to 50 days in some producers, but not at all in others. Meanwhile, there was support for variation in the slope of daily dead weight gain on fibrosis score among both breeds and producers, with some unaffected by high fluke scores and some breeds and producers experiencing a 20g/day lower weight gain under high fluke scores. Our results point to the potential for both environmental and genetic variation in tolerance of liver fluke in cattle, paving the way for quantitative genetic and nutritional research into the feasibility of promoting tolerance as a disease mitigation strategy. ImplicationsPromoting tolerance of disease could help mitigate the impact of disease on livestock productivity, but little research has explored variation in tolerance of livestock diseases or the possibility of promoting tolerance as a mitigation strategy. We used abattoir data to demonstrate that beef cattle vary in their tolerance of fluke infection: while animals from some breeds and some producers experience no impact of fluke on production, others show a large negative effect. Thus, promoting tolerance through management and/or selective breeding could offer a means of reducing the impact of liver fluke on cattle performance.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Hayward, A., Skuce, P. J., McNeilly, T. N.. 2020-07-29. Tolerance of liver fluke infection varies between breeds and producers in Scottish beef cattle. https://doi.org/10.1101/2020.07.29.226894

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

NAE1-Dependent Protein Neddylation Preserves Endothelial Identity and Vascular Integrity

Background: Endothelial dysfunction is a central driver of cardiovascular and inflammatory diseases, yet the post-translational mechanisms that preserve endothelial homeostasis remain incompletely understood. Protein neddylation, the covalent conjugation of a ubiquitin-like modifier, regulates diverse cellular processes, yet its physiological role in the vascular endothelium remains unknown. This study investigated whether protein neddylation is required to preserve endothelial identity and vascular homeostasis. Methods: We generated tamoxifen-inducible endothelial-specific Nae1 knockout mice to inhibit neddylation and combined bulk RNA sequencing, single-cell and single-nucleus transcriptomics, quantitative proteomics, biochemical analyses, and gain- and loss-of-function approaches to define the role of endothelial neddylation in vascular homeostasis and inflammatory injury. Results: Endothelial-specific Nae1 deletion caused rapid mortality associated with vascular leakage, platelet accumulation, inflammation, and multi-organ injury. Multi-omics analyses demonstrated profound loss of endothelial identity, characterized by suppression of core endothelial programs and activation of inflammatory, procoagulant, and pyroptotic pathways. Single-cell analyses revealed progressive endothelial dysfunction culminating in depletion of the endothelial population and remodeling of the vascular niche. Mechanistically, endothelial neddylation deficiency activated gasdermin D (GSDMD)- and gasdermin E (GSDME)-dependent pyroptosis, whereas dual inhibition of GSDMD and GSDME markedly attenuated inflammatory transcriptomic remodeling, vascular injury, hepatocyte death, immune cell infiltration, and platelet accumulation. Translational analyses demonstrated reduced endothelial neddylation in experimental endotoxemia and decreased expression of neddylation pathway components in human atherosclerosis and COVID-19 datasets. Conversely, restoration of endothelial neddylation partially reversed inflammatory endothelial transcriptomic reprogramming in vivo. Conclusions: NAE1-dependent protein neddylation is an essential regulator of endothelial identity and vascular integrity. Loss of endothelial neddylation promotes gasdermin-dependent pyroptosis and thrombo-inflammatory vascular injury, whereas restoration of the neddylation pathway mitigates inflammatory endothelial dysfunction. These findings identify endothelial neddylation as a fundamental mechanism maintaining vascular homeostasis and a potential therapeutic target for cardiovascular and inflammatory diseases.

pathology

Small Vessel Diseases: 3D Characteristics of the Vasculature and White Matter

Cerebral small vessel disease (SVD) is associated with white matter hyperintensities (WMHs), thereby contributing to vascular dementia and movement disorder. However, the pathomechanisms responsible for WMH-related small vessel degeneration remain poorly understood due to the technical limitations of current methods. The aim of this study was to clarify the 2- and 3-dimensional (2D and 3D) pathological features of small vessels and white matter (WM) in the brains of patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), HTRA1-autosomal dominant disease (HTRA1-AD) and sporadic SVD (sSVD). From a cohort of 86 consecutive autopsied patients with SVDs, we retrieved those with genetically confirmed CADASIL and HTRA1-AD (three and three, respectively), and four with sSVD. We quantitatively evaluated WM and vascular changes in the frontal portion of the centrum semiovale and temporal lobe using conventional 2D and chemically cleared 3D analytical methods with light-sheet fluorescence microscopy. Quantitatively, the WM pathology, including the density of myelin, axons and gliosis, was most severe in CADASIL, but unexpectedly sSVD was second in order of severity, followed by HTRA1-AD. The density of clasmatodendrocytes, known to be irreversibly injured astrocytes, was considerably highest in HTRA1-AD. The vascular pathology, including arteriole and capillary sclerosis and the extent of the perivascular space, was most severe in CADASIL, whereas the density of smooth muscle actin (SMA) positivity was most decreased in HTRA1-AD. 3D immunohistochemistry for SMA demonstrated two distinct patterns of SMA loss within the vessels: (1) CADASIL and sSVD: diffuse loss, being prominent in small branches, (2) HTRA1-AD: selective loss in main branches. Overall, the extent of WM and vascular degeneration is most severe in CADASIL, whereas SMA loss is most evident in HTRA1-AD. These differences in the size and distribution of affected vessels may be related to the heterogeneous WM pathology and underlying pathomechanisms of SVD.

pathology

Plant lipid metabolism in susceptible and tolerant soybean (Glycine max) cultivars in response to Phytophthora sojae colonization and infection

Soybean is one of the most cultivated crops globally and a staple food for much of the worlds population. The annual global crop losses due to infection by the Phytophthora sojae are currently estimated at approximately $2B USD, yet we have limited understanding of the role of lipid metabolism in the adaptative strategies used to limit infection and crop loss. We employed a multi-modal lipidomics approach to investigate how soybean cultivars remodel their lipid metabolism to successfully limit infection by Phytophthora sojae. Both the tolerant and susceptible soybean cultivars showed alterations in lipid metabolism in response to Phytophthora sojae infection. Relative to non-inoculated controls, induced accumulation of stigmasterol was observed in the susceptible cultivar whereas, induced accumulation of phospholipids and glycerolipids occurred in tolerant soybean cultivar. We have generated a comprehensive metabolic map of susceptible and tolerant soybean root and stem lipid metabolism to identify lipid modulators of host immune or tolerance response to Phytophthora sojae infection and identified potential pathways and unique lipid biomarkers like TG(15:0/22:0/22:5), TG(10:0/10:0/10:0), TG(10:0/10:0/14:0), DG(18:3/18:3), DG(16:0/18:3) and DG(24:0/18:2) as possible targets for the development of future plant protection solutions.

pathology