Transcriptomic analysis of bovine peripheral blood mononuclear cells stimulated with whole cell lysates from bovine digital dermatitis associated treponemes.

Bovine digital dermatitis (BDD) is an infectious disease in cattle associated with multiple Treponema species yet information on the immune responses of circulating immune cells to these pathogens are limited. In this study, we characterized the transcriptomic responses of bovine peripheral blood mononuclear cells (PBMCs) following stimulation with combined whole cell lysates derived from three BDD-associated Treponema species. PBMCs were stimulated for 12 h and differentially expressed genes between non-stimulated control and stimulated groups were identified. Functional enrichment of DEGs was assessed using Gene Ontology (GO). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed to provide a functional annotation of DEGs. A total of 3458 DEGs were identified, including 1770 upregulated and 1688 downregulated genes (BH-FDR adjusted p-value < 0.05). Notable upregulated genes included IFNγ, CXCL10, IL17F, IL1B, IL6, MMP9, and MMP14 linked to Th1 and Th17 responses, pro-inflammatory cytokine production and extracellular matrix (ECM) remodeling. In contrast, genes associated with antimicrobial activity, complement regulation, and immune modulation, such as LYZ, KLF4, CFD, and NR4A3, were markedly downregulated suggesting suppression of innate immune response and regulatory mechanisms potentially favoring a pro-inflammatory state in PBMCs. Enriched pathways included mitogen-activated protein kinase (MAPK) and tumor necrosis factor (TNF) signaling which could be a key driver in pro-inflammatory signaling and ECM processes. The enrichment of the NOD-like receptor pathway indicates that Treponema spp. whole cell lysates may influence inflammasome-associated and non-canonical inflammatory programs. Overall, this study provides valuable information for further exploration of host-pathogen interactions in BDD.