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Transcriptional Profiling of Ileocecal Valve of Holstein Dairy Cows Infected with Mycobacterium avium subsp. Paratuberculosis.

Hempel RJ, Bannantine JP, Stabel JR - PLoS ONE (2016)

Bottom Line: 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.Interpretation of the gene expression data was performed using pathway analysis and gene ontology categories containing multiple differentially expressed genes.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.

View Article: PubMed Central - PubMed

Affiliation: USDA-Agricultural Research Service (ARS), National Animal Disease Center, Ames, Iowa, United States of America.

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.

No MeSH data available.


Related in: MedlinePlus

Top 10 functional networks that are modulated in group comparisons of differentially expressed genes.Functional networks that are modulated in the comparison between A) clinical and uninfected control animals, B) subclinical and uninfected control animals, C) clinical and subclinical animals.
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pone.0153932.g004: Top 10 functional networks that are modulated in group comparisons of differentially expressed genes.Functional networks that are modulated in the comparison between A) clinical and uninfected control animals, B) subclinical and uninfected control animals, C) clinical and subclinical animals.

Mentions: Pathway analysis was performed on all 823 DE genes using the DAVID Functional Annotation tool. This identified an enrichment of genes involved in T-cell and B-cell receptor signaling and the lysosomal pathways (Fig 4A, Table 3). Within the T-cell receptor pathway genes that were differentially expressed included MAPK13/p38, CD3δ, CD40LG, CD45, CBLC, LCK, MAP3K14/NIK, and PD–1. There are a total of 16 DE genes in the T-cell receptor signaling pathway, 11 of which were down-regulated and 5 that were up-regulated in the clinical cows compared to the uninfected control group (Fig 5). There were several DE genes that are common between the T-cell and B-cell receptor signaling pathways. Of the 11 DE genes observed within the B-cell receptor pathway, 3 DE genes were unique: SHIP/INPP5D, Igα/CD79A, and Igβ/CD79B. It is of special note that the Igα and Igβ genes were highly down-regulated in the clinical cows compared to the uninfected controls, as both the T-cell receptor and B-cell receptor signaling pathways are critical for modulating host immune function.


Transcriptional Profiling of Ileocecal Valve of Holstein Dairy Cows Infected with Mycobacterium avium subsp. Paratuberculosis.

Hempel RJ, Bannantine JP, Stabel JR - PLoS ONE (2016)

Top 10 functional networks that are modulated in group comparisons of differentially expressed genes.Functional networks that are modulated in the comparison between A) clinical and uninfected control animals, B) subclinical and uninfected control animals, C) clinical and subclinical animals.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4836751&req=5

pone.0153932.g004: Top 10 functional networks that are modulated in group comparisons of differentially expressed genes.Functional networks that are modulated in the comparison between A) clinical and uninfected control animals, B) subclinical and uninfected control animals, C) clinical and subclinical animals.
Mentions: Pathway analysis was performed on all 823 DE genes using the DAVID Functional Annotation tool. This identified an enrichment of genes involved in T-cell and B-cell receptor signaling and the lysosomal pathways (Fig 4A, Table 3). Within the T-cell receptor pathway genes that were differentially expressed included MAPK13/p38, CD3δ, CD40LG, CD45, CBLC, LCK, MAP3K14/NIK, and PD–1. There are a total of 16 DE genes in the T-cell receptor signaling pathway, 11 of which were down-regulated and 5 that were up-regulated in the clinical cows compared to the uninfected control group (Fig 5). There were several DE genes that are common between the T-cell and B-cell receptor signaling pathways. Of the 11 DE genes observed within the B-cell receptor pathway, 3 DE genes were unique: SHIP/INPP5D, Igα/CD79A, and Igβ/CD79B. It is of special note that the Igα and Igβ genes were highly down-regulated in the clinical cows compared to the uninfected controls, as both the T-cell receptor and B-cell receptor signaling pathways are critical for modulating host immune function.

Bottom Line: 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.Interpretation of the gene expression data was performed using pathway analysis and gene ontology categories containing multiple differentially expressed genes.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.

View Article: PubMed Central - PubMed

Affiliation: USDA-Agricultural Research Service (ARS), National Animal Disease Center, Ames, Iowa, United States of America.

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.

No MeSH data available.


Related in: MedlinePlus