Characterizing the influence of various antimicrobials used for metaphylaxis against bovine respiratory disease on host transcriptome responses

Rebecca A Bigelow; John T Richeson; Molly McClurg; Robert Valeris-Chacin; Paul S Morley; Jenna L Funk; Matthew A Scott

doi:10.3389/fvets.2023.1272940

Characterizing the influence of various antimicrobials used for metaphylaxis against bovine respiratory disease on host transcriptome responses

Front Vet Sci. 2023 Oct 5:10:1272940. doi: 10.3389/fvets.2023.1272940. eCollection 2023.

Authors

Rebecca A Bigelow¹, John T Richeson¹, Molly McClurg², Robert Valeris-Chacin², Paul S Morley², Jenna L Funk², Matthew A Scott²

Affiliations

¹ Department of Agricultural Sciences, West Texas A&M University, Canyon, TX, United States.
² Veterinary, Education, Research, and Outreach Program, School of Veterinary Medicine and Biomedical Sciences, Texas A&M University, Canyon, TX, United States.

Abstract

Currently, control against bovine respiratory disease (BRD) primarily consists of mass administration of an antimicrobial upon arrival to facility, termed "metaphylaxis." The objective of this study was to determine the influence of six different antimicrobials used as metaphylaxis on the whole blood host transcriptome in healthy steers upon and following arrival to the feedlot. One hundred and five steers were stratified by arrival body weight (BW = 247 ± 28 kg) and randomly and equally allocated to one of seven treatments: negative control (NC), ceftiofur (CEFT), enrofloxacin (ENRO), florfenicol (FLOR), oxytetracycline (OXYT), tildipirosin (TILD), or tulathromycin (TULA). On day 0, whole blood samples and BW were collected prior to a one-time administration of the assigned antimicrobial. Blood samples were collected again on days 3, 7, 14, 21, and 56. A subset of cattle (n = 6) per treatment group were selected randomly for RNA sequencing across all time points. Isolated RNA was sequenced (NovaSeq 6,000; ~35 M paired-end reads/sample), where sequenced reads were processed with ARS-UCD1.3 reference-guided assembly (HISAT2/StringTie2). Differential expression analysis comparing treatment groups to NC was performed with glmmSeq (FDR ≤ 0.05) and edgeR (FDR ≤ 0.1). Functional enrichment was performed with KOBAS-i (FDR ≤ 0.05). When compared only to NC, unique differentially expressed genes (DEGs) found within both edgeR and glmmSeq were identified for CEFT (n = 526), ENRO (n = 340), FLOR (n = 56), OXYT (n = 111), TILD (n = 3,001), and TULA (n = 87). At day 3, CEFT, TILD, and OXYT shared multiple functional enrichment pathways related to T-cell receptor signaling and FcεRI-mediated NF-kappa beta (kB) activation. On day 7, Class I major histocompatibility complex (MHC)-mediated antigen presentation pathways were enriched in ENRO and CEFT groups, and CEFT and FLOR had DEGs that affected IL-17 signaling pathways. There were no shared pathways or Gene Ontology (GO) terms among treatments at day 14, but TULA had 19 pathways and eight GO terms enriched related to NF- κβ activation, and interleukin/interferon signaling. Pathways related to cytokine signaling were enriched by TILD on day 21. Our research demonstrates immunomodulation and potential secondary therapeutic mechanisms induced by antimicrobials commonly used for metaphylaxis, providing insight into the beneficial anti-inflammatory properties antimicrobials possess.

Keywords: RNA-Seq; T-cell; antimicrobial; bovine respiratory disease; cattle; immune; metaphylaxis; transcriptome.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was internally funded in part by Texas A&M University, School of Veterinary Medicine and Biomedical Sciences and West Texas A&M University, Department of Agricultural Sciences. Additionally, this study was externally funded in part by the Texas Cattle Feeders Association (TCFA).