Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 10/23/2007
Publication Date: 10/23/2007
Citation: Paustian, M., Janagama, H.K., Motiwala, A.S., Sreevatsan, S., Bannantine, J.P. 2007. Macrophage Transcriptional Response to Species-Adapted Mycobacterium avium subsp. Paratuberculosis Isolates: The Role of Pathogen Genotype in Host Response [abstract]. Abstract No. PA-072. p. 59. Interpretive Summary: This work examined the changes in immune system gene expression in response to several different isolates of Mycobacterium avium subsp. paratuberculosis, which is the bacterium that causes Johne’s Disease. The study revealed that changes in the genome of bacteria were reflected by changes in the response of cells that were infected with the bacteria. The findings of this work should be of interest to other scientists studying Johne’s Disease as well as researchers studying other host-pathogen interactions.
Technical Abstract: The transcriptional response of human and bovine macrophages to Mycobacterium avium subsp. paratuberculosis (M. paratuberculosis) isolates from cattle and sheep were examined using DNA microarrays. M. paratuberculosis is the etiologic agent of Johne’s Disease, a chronic infection of ruminant animals characterized by inflammation of the digestive tract leading to nutrient malabsorption and eventually death. Comparative genomic microarray hybridizations were used to identify large sequence polymorphisms (LSPs) in the genomes of M. paratuberculosis cattle and sheep isolates. Relative to cattle isolates, M. paratuberculosis sheep isolates are missing 33 genes and have gained an additional 77 genes that are homologous to sequences in the Mycobacterium avium subsp. avium genome. The M. paratuberculosis sheep and cattle isolates were used to infect a human monocytic cell line (THP-1 cells) as well as bovine monocyte derived macrophages obtained from an uninfected host. The transcriptional response of THP-1 cells was monitored using Human Genome U133 Affymetrix GeneChip microarrays, which identified 37 and 4,780 differentially transcribed genes in cells stimulated with M. paratuberculosis cattle or sheep isolates, respectively. The functional pathways included in these gene sets indicate that M. paratuberculosis sheep isolates induce a pro-inflammatory response that is not observed for cattle isolates. An analysis of the bovine macrophage transcriptional response to these isolates using whole-genome 70mer oligonucleotide microarrays is ongoing in order to determine the extent of differential transcription in the natural host. These results highlight the role that pathogen genotypes play in host response and provide insights into the genetic determinants of species specificity.