Department of Veterinary Clinical Sciences, Field Disease Investigation Unit, Washington State University, Pullman, Washington, United States of America.
PLoS One. 2023 May 16;18(5):e0285876. doi: 10.1371/journal.pone.0285876. eCollection 2023.
Bovine respiratory disease (BRD) is a leading cause of calf morbidity and mortality, and prevalence remains high despite current management practices. Differential gene expression (DGE) provides detailed insight into individual immune responses and can illuminate enriched pathways and biomarkers that contribute to disease susceptibility and outcomes. The aims of this study were to investigate differences in peripheral leukocyte gene expression in Holstein preweaned heifer calves 1) with and without BRD, and 2) across weeks of age. Calves were enrolled for this short-term longitudinal study on two commercial dairies in Washington State. Calves were assessed every two weeks throughout the pre-weaning period using clinical respiratory scoring (CRS) and thoracic ultrasonography (TUS), and blood samples were collected. Calves were selected that were either healthy (n = 10) or had BRD diagnosed by CRS (n = 7), TUS (n = 6), or both (n = 6) in weeks 5 or 7 of life). Three consecutive time point samples were analyzed for each BRD calf consisting of PRE, ONSET, and POST samples. Nineteen genes of interest were selected based on previous gene expression studies in cattle: ALOX15, BPI, CATHL6, CXCL8, DHX58, GZMB, HPGD, IFNG, IL17D, IL1R2, ISG15, LCN2, LIF, MX1, OAS2, PGLYRP1, S100A8, SELP, and TNF. Comparisons were made between age and disease time point matched BRD and healthy calves as well as between calf weeks of age. No DGE was observed between diseased and healthy calves; however, DGE was observed between calf weeks of age regardless of disease state. Developmental differences in leukocyte gene expression, phenotype, and functionality make pre-weaned calves immunologically distinct from mature cattle, and early life shifts in calf leukocyte populations likely contribute to the age-related gene expression differences we observed. Age overshadows disease impacts to influence gene expression in young calves, and immune development progresses upon a common trajectory regardless of disease during the preweaning period.
牛呼吸道疾病 (BRD) 是导致犊牛发病率和死亡率的主要原因，尽管目前采用了管理措施，但该病的流行率仍然很高。差异基因表达 (DGE) 可提供对个体免疫反应的详细了解，并可阐明导致疾病易感性和结果的富集途径和生物标志物。本研究的目的是研究荷斯坦未断奶小母牛犊牛 1）有无 BRD 以及 2）在不同周龄时外周白细胞基因表达的差异。本研究在华盛顿州的两个商业奶牛场进行了这项短期纵向研究，对犊牛进行了招募。在整个未断奶期间，每隔两周通过临床呼吸评分 (CRS) 和胸部超声 (TUS) 对犊牛进行评估，并采集血液样本。选择健康的犊牛（n = 10）或在第 5 或 7 周龄时通过 CRS（n = 7）、TUS（n = 6）或两者（n = 6）诊断为 BRD 的犊牛。对于每只 BRD 犊牛，有三个连续时间点的样本进行分析，包括 PRE、ONSET 和 POST 样本。基于以前在牛中的基因表达研究，选择了 19 个感兴趣的基因：ALOX15、BPI、CATHL6、CXCL8、DHX58、GZMB、HPGD、IFNG、IL17D、IL1R2、ISG15、LCN2、LIF、MX1、OAS2、PGLYRP1、S100A8、SELP 和 TNF。比较了年龄和疾病时间点相匹配的 BRD 与健康犊牛之间以及犊牛周龄之间的差异。未观察到患病和健康犊牛之间的基因差异；然而，无论疾病状态如何，都观察到了犊牛周龄之间的基因差异。白细胞基因表达、表型和功能的发育差异使未断奶的犊牛在免疫学上与成熟牛不同，并且在犊牛白细胞群体中早期的生命转变可能导致我们观察到的与年龄相关的基因表达差异。年龄掩盖了疾病对幼犊基因表达的影响，并且在未断奶期间，免疫发育沿着共同的轨迹进行，而与疾病无关。
