Disease & heat resistance

Challenging bovine fibroblasts from heifers with divergent genetic merit for digital dermatitis resistance reveals distinct transcriptional responses

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Abstract

Abstract Text: Digital dermatitis (DD) is a painful, infectious, polybacterial disease that is one of the primary causes of lameness in dairy cattle. DD is critical for the dairy industry due to associations with reduced milk yield, decreased reproductive performance, and early replacement. Treponema spp. plays a key role in the pathogenesis of DD. Although the presence of host genetic resistance to DD is known, the molecular and genetic mechanisms underlying it are still not fully understood. The aim of this study was to investigate whether primary fibroblasts obtained from heifers with different genomic estimated breeding values (GEBVs) for DD resistance exhibited different transcriptional responses when exposed to sonicated Treponema spp. stimuli.A total of 323 maiden heifers were monitored over four months, and their hind feet were assessed for DD presence according to the M-stage system. GEBVs related to DD resistance were obtained from the official UK national evaluation database (AHDB, 2020). High and low GEBVs indicate genetically resistant and susceptible individuals, respectively. Based on genetic merit and DD clinical history, 15 heifers were selected to represent three groups: five heifers with high-GEBV that were healthy (HGH), five heifers with low-GEBV that were infected then healed (LGIH), and five heifers with low-GEBV that were chronically infected (LGCI). Primary foot skin fibroblast cultures were obtained from biopsies of the selected groups. Fibroblasts cells monolayers were co-incubated for six hours with control media, Salmonella Typhimurium lipopolysaccharide (LPS), sonicated Treponema phagedenis extract (T320A), and sonicated Treponema mix (Treponema pedis, T. medium, T. phagedenis). Subsequently, RNA samples extracted from the cells were sent for bulk RNA sequencing. Pairwise comparisons between treatments and groups were performed on the RNA-Seq data, resulting in a total of 27 contrasts to identify differentially expressed genes (DEGs).Principal component analysis showed treatment was the main source of variation, while genetic merit and DD status also contributed. Analysis of 27 pairwise contrasts identified between 1 and 1,789 DEGs per comparison (padj ≤ 0.05, |log2FC| ≥ 1), highlighting substantial variation in transcriptional responses among experimental groups. Fibroblasts from LGIH and LGCI exhibited a greater number of DEGs compared with those from the HGH, suggesting that susceptible animals display broader or less regulated transcriptional responses. Pathway analyses revealed enrichment of immune response, Toll-like receptor activation, cytokine-mediated signaling, extracellular matrix organization, and wound-healing processes.Genetic merit for DD resistance may be reflected in basal and induced transcriptional responses of foot-skin primary fibroblasts exposed to sonicated Treponema spp. Variations in immune activation genes and inflammatory pathways might contribute to differences in the host's ability to resist or heal DD lesions. These findings provide novel insights into genetic resistance to DD by elucidating host-pathogen interactions and support breeding strategies to improve cattle health, welfare and productivity.

Keywords: 2026

How to Cite:

Sato, A., Bao, K., Anagnostopoulos, A., Kaya, B., Siachos, N., Gillespie, A., Liu, X., Werling, D., Banos, G., Psifidi, A., Evans, N. & Oikonomou, G., (2026) “Challenging bovine fibroblasts from heifers with divergent genetic merit for digital dermatitis resistance reveals distinct transcriptional responses”, World Congress on Genetics Applied to Livestock Production Digital Archive 2026(1): 2286374. doi: https://doi.org/10.31274/wcgalp.23967

Rights: 1