Tissue Tropism in Host Transcriptional Response to Members of the Bovine Respiratory Disease Complex

Susanta K Behura,Robert D Schnabel,Christopher M Seabury,Holly L Neibergs,Jeremy F Taylor,Laurel J Gershwin,Luciana C A Regitano,Alison L Van Eenennaam,Jaewoo Kim,Rachel Toaff-Rosenstein,Polyana C Tizioto,Natalia V Grupioni

doi:10.1038/s41598-017-18205-0

Abstract

Bovine respiratory disease (BRD) is the most common infectious disease of beef and dairy cattle and is characterized by a complex infectious etiology that includes a variety of viral and bacterial pathogens. We examined the global changes in mRNA abundance in healthy lung and lung lesions and in the lymphoid tissues bronchial lymph node, retropharyngeal lymph node, nasopharyngeal lymph node and pharyngeal tonsil collected at the peak of clinical disease from beef cattle experimentally challenged with either bovine respiratory syncytial virus, infectious bovine rhinotracheitis, bovine viral diarrhea virus, Mannheimia haemolytica or Mycoplasma bovis. We identified signatures of tissue-specific transcriptional responses indicative of tropism in the coordination of host’s immune tissue responses to infection by viral or bacterial infections. Furthermore, our study shows that this tissue tropism in host transcriptional response to BRD pathogens results in the activation of different networks of response genes. The differential crosstalk among genes expressed in lymphoid tissues was predicted to be orchestrated by specific immune genes that act as ‘key players’ within expression networks. The results of this study serve as a basis for the development of innovative therapeutic strategies and for the selection of cattle with enhanced resistance to BRD.

Highlights

Bovine respiratory disease (BRD) is the most common infectious disease of beef and dairy cattle and is characterized by a complex infectious etiology that includes a variety of viral and bacterial pathogens
We examined the global changes in mRNA abundance in healthy lung and lung lesions and in the lymphoid tissues bronchial lymph node, retropharyngeal lymph node, nasopharyngeal lymph node and pharyngeal tonsil collected at the peak of clinical disease from beef cattle experimentally challenged with either bovine respiratory syncytial virus, infectious bovine rhinotracheitis, bovine viral diarrhea virus, Mannheimia haemolytica or Mycoplasma bovis
Transcript abundance differences between challenged and control animals were estimated for samples derived from lung lesion (LNGL) and four lymphoid tissues: bronchial lymph node (BLN), retropharyngeal lymph node (RLN), nasopharyngeal lymph node (NLN) and pharyngeal tonsil (PGT)

Summary

Introduction

Bovine respiratory disease (BRD) is the most common infectious disease of beef and dairy cattle and is characterized by a complex infectious etiology that includes a variety of viral and bacterial pathogens. Our study shows that this tissue tropism in host transcriptional response to BRD pathogens results in the activation of different networks of response genes. Bovine respiratory disease (BRD) is the most common infectious disease of beef and dairy cattle and is responsible for 70–80% of morbidities and 40–50% of feedlot cattle mortalities in the United States[1]. BRD is a multifactorial disorder with a complex infectious etiology involving several viral and bacterial pathogens collectively referred to as the bovine respiratory disease complex (BRDC). Vaccines and antimicrobials have not been effective in decreasing BRD morbidity or mortality rates and BRD remains prevalent despite being widely studied[5]

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