@article { , title = {Associations between Circulating IGF-1 Concentrations and Disease Status with the Leukocyte Transcriptome in Early Lactation Dairy Cows}, abstract = {Peripartum dairy cows commonly experience negative energy balance (EB) and immunosuppression together with high incidences of infectious and metabolic disease. This study investigated mechanisms linking EB status with immune defence in early lactation. Data were collected from multiparous Holstein cows from six herds and leukocyte transcriptomes were analysed using RNA sequencing. Global gene expression was related to circulating IGF-1 (as a biomarker for EB) by subdividing animals into three groups, defined as IGF-1 LOW (100 ng/ml, n=43) at 14 ± 4 days in milk (DIM). Differentially expressed genes between groups were identified using CLC Genomics Workbench V21, followed by cluster and KEGG pathway analysis, focussing on the comparison between LOW and HIGH IGF-1 cows. LOW cows were older and had significantly lower dry matter intakes and EB values, whereas HIGH cows produced more milk. During the first 35 DIM, 71\% of LOW cows had more than one health problem v 26\% HIGH cows, including more with clinical mastitis and uterine infections. Gene expression analysis indicated that leukocytes in LOW cows switched energy metabolism from oxidative phosphorylation to aerobic glycolysis (PGM, LDH, PDK4). Many antimicrobial peptides were up-regulated in LOW cows (e.g. PTX3, DMBT1, S100A8, S100A9) together with genes associated with inflammation, platelet activation and the complement cascade. HIGH cows had greater expression of genes regulating T and B cell function and the cytoskeleton. Overall results suggested an ongoing cycle of poor EB and higher infection rates in LOW IGF-1 cows which was reflected in altered leukocyte functionality and reduced milk production.}, journal = {Ruminants}, publicationstatus = {Published}, publisher = {MDPI}, url = {https://rvc-repository.worktribe.com/output/1551607}, year = {2021}, author = {Wathes, D Claire and Becker, Frank and Buggiotti, Laura and Crowe, Mark A and Ferris, Conrad and Foldager, Leslie and Grelet, Clément and Hostens, Miel and Ingvartsen, Klaus L and Marchitelli, Cinzia and Salavati, Mazdak and Signorelli, Federica and Takeda, Haruko and Tang, Lijing and Cheng, Zhangrui and GplusE consortium,} }