Immunological Response to Single Pathogen Challenge with Agents of the Bovine Respiratory Disease Complex: An RNA-Sequence Analysis of the Bronchial Lymph Node Transcriptome

Abstract

Susceptibility to bovine respiratory disease (BRD) is multi-factorial and is influenced by stress in conjunction with infection by both bacterial and viral pathogens. While vaccination is broadly used in an effort to prevent BRD, it is far from being fully protective and cases diagnosed from a combination of observed clinical signs without any attempt at identifying the causal pathogens are usually treated with antibiotics. Dairy and beef cattle losses from BRD are profound worldwide and genetic studies have now been initiated to elucidate host loci which underlie susceptibility with the objective of enabling molecular breeding to reduce disease prevalence. In this study, we employed RNA sequencing to examine the bronchial lymph node transcriptomes of controls and beef cattle which had individually been experimentally challenged with bovine respiratory syncytial virus, infectious bovine rhinotracheitis, bovine viral diarrhea virus, Pasteurella multocida, Mannheimia haemolytica or Mycoplasma bovis to identify the genes that are involved in the bovine immune response to infection. We found that 142 differentially expressed genes were located in previously described quantitative trait locus regions associated with risk of BRD. Mutations affecting the expression or amino acid composition of these genes may affect disease susceptibility and could be incorporated into molecular breeding programs. Genes involved in innate immunity were generally found to be differentially expressed between the control and pathogen-challenged animals suggesting that variation in these genes may lead to a heritability of susceptibility that is pathogen independent. However, we also found pathogen-specific expression profiles which suggest that host genetic variation for BRD susceptibility is pathogen dependent.

Comprehensive RNA-Seq Profiling to Evaluate the Sheep Mammary Gland Transcriptome in Response to Experimental Mycoplasma agalactiae Infection

“…Gene expression profiling has been intensively used for several mycoplasma species to study host-pathogen interactions. In this context, the transcriptomes of either the host or the pathogen were investigated to gain further insights into mycoplasma-induced pathogenesis [40–44]. To the best of our knowledge this is a singular study in many aspects.…”

Bovine respiratory syncytial virus infection enhances Pasteurella multocida adherence on respiratory epithelial cells

“…BRDC often occurs in cattle that are stressed; this is often coincident with natural exposure to viral and bacterial agents and results in clinical signs and lung pathology (Tizioto et al, 2015). In addition, the presence of more than one microorganism in the respiratory tract can lead to more severe pneumonia (Larsen et al, 2001;Klima et al, 2014).…”

“…BRDC is caused by an interaction between viral and bacterial pathogens; infectious agents include bovine herpesvirus, bovine viral diarrhea virus, bovine parainfluenza-3 virus, Pasteurella multocida (PM), Mannheimia haemolytica, Mycoplasma bovis, and Histophilus somni (Larsen et al, 2001;Tizioto et al, 2015). Each pathogen harbors unique features that enable it to act as either a primary source of infection or as a partner in cases of multi-pathogen infection; such infections compromise the protective barrier function of the respiratory epithelium (Härtel et al, 2004;Gershwin et al, 2005).…”

The Immunology of Bovine Respiratory Disease

“…4 A transcriptome analysis of the bronchial lymph nodes of calves singly infected with BRD pathogens revealed a global up-regulation of many PRR-associated genes, although there was some specificity in the response to particular pathogens. 5 Although M haemolytica infection induced selective up-regulation of TLR1 and TLR6, infection with BHV-1, bovine respiratory syncytial virus (BRSV) or bovine viral diarrhea virus (BVDV) induced more pronounced up-regulation of TLR2 and TLR4. 5 The biological significance of these differences is not immediately clear but warrants further investigation.…”

“…5 Although M haemolytica infection induced selective up-regulation of TLR1 and TLR6, infection with BHV-1, bovine respiratory syncytial virus (BRSV) or bovine viral diarrhea virus (BVDV) induced more pronounced up-regulation of TLR2 and TLR4. 5 The biological significance of these differences is not immediately clear but warrants further investigation. In an in vitro coinfection model, exposure of alveolar type 2 epithelial cells to Histophilus somni induced activation of the type I interferon (IFN) response, which subsequently protected the cells from BRSV infection.…”