Severity of bovine tuberculosis is associated with innate immune-biased transcriptional signatures of whole blood in early weeks after experimental Mycobacterium bovis infection

• Published in: PloS one 2020-11, Vol.15 (11), p.e0239938-e0239938
• Main Authors: Wiarda, Jayne E, Boggiatto, Paola M, Bayles, Darrell O, Waters, W Ray, Thacker, Tyler C, Palmer, Mitchell V
• Format: Article
• Language: English
• Subjects: Aerosols; Agricultural research; Animal diseases; Animals; Biological activity; Biology and Life Sciences; Blood; Bovine tuberculosis; Cattle; Development and progression; Gene expression; Gene Expression - genetics; Gene Expression Profiling - veterinary; Genetic aspects; Immunity, Innate - genetics; Infections; Leukocytes, Mononuclear - cytology; Leukocytes, Mononuclear - metabolism; Lymphatic system; Medicine and Health Sciences; Mycobacterium bovis; Mycobacterium bovis - genetics; Mycobacterium bovis - immunology; Oligonucleotide Array Sequence Analysis; Research and analysis methods; Ribonucleic acid; RNA; Severity of Illness Index; Transcription; Transcription (Genetics); Transcriptome - genetics; Tuberculosis; Tuberculosis, Bovine - immunology; Tuberculosis, Bovine - pathology; Veterinary research; Virulence
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0239938

Mycobacterium bovis, the causative agent of bovine tuberculosis, is a pathogen that impacts both animal and human health. Consequently, there is a need to improve understanding of disease dynamics, identification of infected animals, and characterization of the basis of immune protection. This study assessed the transcriptional changes occurring in cattle during the early weeks following a M. bovis infection. RNA-seq analysis of whole blood-cell transcriptomes revealed two distinct transcriptional clusters of infected cattle at both 4- and 10-weeks post-infection that correlated with disease severity. Cattle exhibiting more severe disease were transcriptionally divergent from uninfected animals. At 4-weeks post-infection, 25 genes had commonly increased expression in infected cattle compared to uninfected cattle regardless of disease severity. Ten weeks post-infection, differential gene expression was only observed when severely-affected cattle were compared to uninfected cattle. This indicates a transcriptional divergence based on clinical status following infection. In cattle with more severe disease, biological processes and cell type enrichment analyses revealed overrepresentation of innate immune-related processes and cell types in infected animals. Collectively, our findings demonstrate two distinct transcriptional profiles occur in cattle following M. bovis infection, which correlate to clinical status.