Transcriptional profiling of ileocecal valve of Holstein dairy cows infected with mycobacterium avium subsp. paratuberculosis

Authors: Hempel, Randy; Bannantine, John; Stabel, Judith

Submitted to: PLOS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/6/2016
Publication Date: 4/19/2016
Citation: Hempel, R.J., Bannantine, J.P., Stabel, J.R. 2016. Transcriptional profiling of ileocecal valve of Holstein dairy cows infected with mycobacterium avium subsp. paratuberculosis. PLoS One. 11(4):E0153932. doi:10.1371/journal.pone.0153932.

Interpretive Summary: Johne's disease is a chronic, debilitating intestinal disorder in cattle characterized by diarrhea, reduced feed intake, weight loss and death. Cattle usually become infected as young calves by ingesting feces containing the causative bacteria. However, symptoms of disease do not usually present themselves until the animals reach 3 to 5 years of age or even older. During this time the animal is infected and may be shedding the organism in its feces without showing any clinical signs of disease. In addition to reduced production by these animals through reduced milk production, they also present a potential infective threat to the rest of the herd. New tools to diagnose and control Johne’s disease are essential to prevent further economic hardship within the livestock industry. The current study utilized sequencing methods to identify genes that are expressed in the tissue of infected cattle in different stages of disease and compare them to gene expression in noninfected cattle. These results suggest that major differences in gene expression are present between cows with clinical disease and noninfected cows. These data provide information as to biomarkers of disease that can be used to improve diagnostic tools.

Technical Abstract: Johne’s disease is a chronic infection of the small intestine caused by Mycobacterium avium subspecies paratuberculosis (MAP), an intracellular bacterium. The events of pathogen survival within the host cell(s), chronic inflammation and the progression from asymptomatic subclinical stage to an advanced clinical stage of infection, are poorly understood. This study examines gene expression in the ileocecal valve (ICV) of Holstein dairy cows at different stages of MAP infection. The ICV is known to be a primary site of MAP colonization and provides an ideal location to identify genes that are relevant to the progression of this disease. RNA was prepared from ICV tissues and RNA-Seq was used to compare gene transcription between clinical, subclinical, and uninfected control animals. Interpretation of the gene expression data was performed using pathway analysis and gene ontology categories containing multiple differentially expressed genes. Results demonstrated that many of the pathways that had strong differential gene expression between uninfected control and clinical cows were related to the immune system, such as the T- and B-cell receptor signaling, apoptosis, NOD-like receptor signaling, and leukocyte transendothelial migration pathways. In contrast, the comparison of gene transcription between control and subclinical cows identified pathways that were primarily involved in metabolism. The results from the comparison between clinical and subclinical animals indicate recruitment of neutrophils, up regulation of lysosomal peptidases, increase in immune cell transendothelial migration, and modifications of the extracelluar matrix. This study provides important insight into how cattle respond to a natural MAP infection at the gene transcription level within a key target tissue for infection.