Omics & gene networks

Exploring Genetic Factors and Potential Pathways Involved in Regulatory Networks of Monocyte Inflammatory Responses to Bovine Mastitis Caused by Streptococcus uberis

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Abstract

Mastitis is a major global disease in dairy cattle, adversely affecting animal health, milk quality, and the economics of milk production. The National Mastitis Council estimates the total cost to the dairy industry exceeds $2 billion annually, ~ $180 per cow. Despite extensive research, the pathogen-specific regulatory mechanisms underlying host immune responses remain incompletely understood, particularly at the level of circulating immune cells. Therefore, the objective of this study was to investigate gene regulatory mechanisms involved in host immune responses to mastitis by integrating comparative transcriptome profiling with miRNA-mRNA regulatory network analysis in blood FACS-isolated CD14⁺ monocytes from healthy cows and cows naturally affected by subclinical intramammary infections caused by Streptococcus uberis (Strep. uberis). Publicly available RNA sequencing (RNA-Seq) datasets from blood FACS-isolated CD14⁺ monocytes of healthy (n = 57) and mastitic (n = 58) Holstein dairy cattle were retrieved from the NCBI Gene Expression Omnibus (GEO) database (accessions GSE51858, GSE172056, and GSE220666). After quality control and differential expression analysis, transcripts were considered significantly differentially expressed using thresholds of |fold change| ≥ 1.5 and a false discovery rate (FDR) ≤ 0.01. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted using the DAVID and STRING databases to identify biological processes, molecular functions, cellular components, and signaling pathways associated with mastitis. Comparative transcriptomic analysis identified 899 differentially expressed genes (DEGs) and 10 differentially expressed miRNAs across the three datasets. Among these, 423 mRNAs and 9 miRNAs were integrated into a reconstructed bipartite miRNA-mRNA regulatory network. Network-based analysis enabled identification of 19 hub genes (CXCL10, IGF1R, VCL, CD68, ALDH18A1, GART, CSF1, CREBBP, DNAJC10, CORO1A, MAP2K1, CDH1, KDR, COX1, ITGAM, MAP2K2, MPO, PLCG2, and STAT4) and five hub miRNAs (bta-miR-126, bta-miR-218, bta-miR-10a, bta-miR-148a, and bta-miR-184). Notably, several of these hub regulators have not previously been highlighted as central components of miRNA-mRNA networks in monocytes during Strep. uberis -associated mastitis, providing added insight beyond individual transcript-level analyses reported in earlier studies. GO and KEGG enrichment analyses revealed that the identified DE RNAs were predominantly associated with immune-related biological processes and signaling pathways, including innate immune response, cytokine and chemokine signaling, JAK-STAT, HIF-1, mTOR, ErbB, and B cell receptor pathways. These findings suggest coordinated transcriptional and post-transcriptional regulation of immune activation, inflammation, and pathways linked to lactation and milk component synthesis during mastitis. Overall, this integrative bioinformatics approach enhances understanding of miRNA-mediated gene regulatory mechanisms in circulating monocytes during mastitis caused by Strep. uberis. Although the identified hub genes and miRNAs represent promising molecular candidates, further validation in larger populations and functional studies are required before these findings can be translated into therapeutic strategies or breeding programs aimed at improving mastitis resistance in dairy cattle.

Keywords: 2026

How to Cite:

Ghafouri, F., Pirkhezranian, S., Dehghanian Reyhan, V., Sadeghi, M., Miraei-Ashtiani, S., Kastelic, J., Barkema, H., Razban, V. & Shirali, M., (2026) “Exploring Genetic Factors and Potential Pathways Involved in Regulatory Networks of Monocyte Inflammatory Responses to Bovine Mastitis Caused by Streptococcus uberis”, World Congress on Genetics Applied to Livestock Production Digital Archive 2026(1): 2286493. doi: https://doi.org/10.31274/wcgalp.24028

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