Susceptibility and Molecular Mechanisms Underlying Bovine Respiratory Disease Complex

Bovine respiratory disease complex (BRDC) is a multi-factorial disease which is typically observed when cattle are exposed to a predisposing stress and a combination of several bacterial and viral pathogens. Losses from BRDC within both the beef and dairy cattle industries are considerable worldwide and genomic studies have now been performed to elucidate the loci which underlie susceptibility to BRDC. These studies are expected to lead to selection programs designed to reduce the prevalence of disease prevalence through the gradual elimination of susceptibility alleles from cattle populations. In this study, RNA sequencing of bronchial lymph node transcriptomes was employed to examine the immune responses of Angus × Hereford controls (N = 3) and six experimental groups (each N = 4) that had been artificially challenged with bovine respiratory syncytial virus, infectious bovine rhinotracheitis, bovine viral diarrhea virus, Pasteurella multocida, Mannheimnia haemolytica and Mycoplasma bovis. Genes commonly involved in innate immune mechanisms were found to be differentially expressed between cases and controls, suggesting that variation in these genes may lead to a heritability of susceptibility that is pathogen independent. However, we also found expression differences in toll-like receptors that recognize specific pathogens via their unique molecular signatures. For M. haemolytica we found TLR1 and TLR6 to be up-regulated in the challenged animals, while TLR2 and TLR4 were up-regulated in the animals challenged with infectious bovine rhinotracheitis. These data provide new insights and perspectives into host genetic susceptibility and the molecular mechanisms underlying BRDC.