Veterinary Education, Research, and Outreach Program, Texas A&M University, Canyon, TX, United States.
Texas A&M Veterinary Medical Diagnostic Laboratory, Canyon, TX, United States.
Front Immunol. 2024 Sep 13;15:1412766. doi: 10.3389/fimmu.2024.1412766. eCollection 2024.
Bovine respiratory disease (BRD) remains the leading infectious disease in beef cattle production systems. Host gene expression upon facility arrival may indicate risk of BRD development and severity. However, a time-course approach would better define how BRD development influences immunological and inflammatory responses after disease occurrences. Here, we evaluated whole blood transcriptomes of high-risk beef cattle at three time points to elucidate BRD-associated host response. Sequenced jugular whole blood mRNA from 36 cattle (2015: = 9; 2017: = 27) across three time points ( = 100 samples; days [D]0, D28, and D63) were processed through ARS-UCD1.2 reference-guided assembly (HISAT2/Stringtie2). Samples were categorized into BRD-severity cohorts (Healthy, = 14; Treated 1, = 11; Treated 2+, = 11) via frequency of antimicrobial clinical treatment. Assessment of gene expression patterns over time within each BRD cohort was modeled through an autoregressive hidden Markov model (EBSeq-HMM; posterior probability ≥ 0.5, FDR < 0.01). Mixed-effects negative binomial models (glmmSeq; FDR < 0.05) and edgeR (FDR < 0.10) identified differentially expressed genes between and across cohorts overtime. A total of 2,580, 2,216, and 2,381 genes were dynamically expressed across time in Healthy, Treated 1, and Treated 2+ cattle, respectively. Genes involved in the production of specialized resolving mediators (SPMs) decreased at D28 and then increased by D63 across all three cohorts. Accordingly, SPM production and alternative complement were differentially expressed between Healthy and Treated 2+ at D0, but not statistically different between the three groups by D63. Magnitude, but not directionality, of gene expression related to SPM production, alternative complement, and innate immune response signified Healthy and Treated 2+ cattle. Differences in gene expression at D63 across the three groups were related to oxygen binding and carrier activity, natural killer cell-mediated cytotoxicity, cathelicidin production, and neutrophil degranulation, possibly indicating prolonged airway pathology and inflammation weeks after clinical treatment for BRD. These findings indicate genomic mechanisms indicative of BRD development and severity over time.
牛呼吸道疾病（BRD）仍然是肉牛生产系统中主要的传染病。在设施到达时的宿主基因表达可能表明 BRD 发展和严重程度的风险。然而，时间过程方法可以更好地定义 BRD 发展如何在疾病发生后影响免疫和炎症反应。在这里，我们在三个时间点评估了高风险肉牛的全血转录组，以阐明与 BRD 相关的宿主反应。对 36 头牛（2015 年：=9；2017 年：=27）在三个时间点（=100 个样本；天 [D]0、D28 和 D63）的颈静脉全血 mRNA 进行了测序，并通过 ARS-UCD1.2 参考指导组装（HISAT2/Stringtie2）进行了处理。通过抗菌药物临床治疗频率将样品分类为 BRD 严重程度队列（健康，=14；治疗 1，=11；治疗 2+，=11）。通过自回归隐马尔可夫模型（EBSeq-HMM；后验概率≥0.5，FDR<0.01）在每个 BRD 队列内随时间评估基因表达模式。混合效应负二项式模型（glmmSeq；FDR<0.05）和 edgeR（FDR<0.10）确定了不同时间点和不同队列之间的差异表达基因。在健康、治疗 1 和治疗 2+牛中，分别有 2580、2216 和 2381 个基因随时间动态表达。所有三个队列中，专门的解决介质（SPM）的产生相关基因在 D28 时减少，然后在 D63 时增加。相应地，在 D0 时，SPM 产生和替代补体在健康和治疗 2+之间存在差异表达，但在 D63 时三组之间没有统计学差异。SPM 产生、替代补体和固有免疫反应相关基因表达的幅度（而非方向性）表明健康和治疗 2+牛。三组之间在 D63 时的基因表达差异与氧结合和载体活性、自然杀伤细胞介导的细胞毒性、cathelicidin 产生和嗜中性粒细胞脱颗粒有关，这可能表明 BRD 临床治疗数周后气道病理和炎症持续存在。这些发现表明了随时间发展和严重程度的 BRD 相关的基因组机制。
