Comprehensive time-course gene expression evaluation of high-risk beef cattle to establish immunological characteristics associated with undifferentiated bovine respiratory disease

Front Immunol. 2024 Sep 13:15:1412766. doi: 10.3389/fimmu.2024.1412766. eCollection 2024.

Abstract

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: n = 9; 2017: n = 27) across three time points (n = 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, n = 14; Treated 1, n = 11; Treated 2+, n = 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.

Keywords: bovine respiratory disease; cattle; immunoglobulin; inflammation; interleukin; major histocompatibility complex; specialized pro-resolving mediators; transcriptome.

MeSH terms

  • Animals
  • Bovine Respiratory Disease Complex* / genetics
  • Bovine Respiratory Disease Complex* / immunology
  • Cattle
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Time Factors
  • Transcriptome

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was supported in part by the US Department of Agriculture, National Institute of Food and Agriculture, Diseases of Agricultural Animals Program (Grant No. 2020-67016-31469). Additionally, this research was internally supported by the Department of Large Animal Clinical Sciences at Texas A&M University College of Veterinary Medicine and Biomedical Sciences, the Department of Pathobiology and Population Medicine at Mississippi State University College of Veterinary Medicine, and the Department of Animal and Dairy Sciences at Mississippi State University. The findings and conclusions in this work have not been formally disseminated by the US Department of Agriculture and should not be construed to represent any agency determination or policy.