title: Expression of genes associated with cholesterol and lipid metabolism identified as a novel pathway in the early pathogenesis of Mycobacterium avium subspecies paratuberculosis-infection in cattle.
abstract: Johne's disease (JD) is a chronic disease affecting ruminants and other species caused by the pathogenic mycobacterium, Mycobacterium avium subsp. paratuberculosis (MAP). MAP has developed a multitude of mechanisms to persist within the host, and these in turn are counteracted by the host through various immune pathways. Identifying and characterising the different strategies employed by MAP to alter the host immune system in its favour, and thereby persist intracellularly, could hold the key to developing strategies to fight this disease. In this study we analysed a subset of bovine microarray data derived from early time points after experimental infection with MAP. A specifically developed integrated approach was used to identify and validate host genes involved in cholesterol homeostasis (24DHCR, LDLR, SCD-1), calcium homeostasis and anti-bacterial defence mechanisms, (CD38, GIMAP6) which were downregulated in response to MAP exposure. A trend for upregulation of granulysin gene expression in MAP-exposed cattle in comparison to unexposed cattle was also observed. From these analyses, a model of potential pathogen-host interactions involving these novel pathways was developed which indicates an important role for host lipids in mycobacterial survival and persistence.
authors.affiliation: Faculty of Veterinary Science, The University of Sydney, 425 Werombi Road, Camden 2570, NSW, Australia.
authors.forename: Shyamala
authors.initials: S
authors.lastname: Thirunavukkarasu
authors.affiliation: Faculty of Veterinary Science, The University of Sydney, 425 Werombi Road, Camden 2570, NSW, Australia.
authors.forename: Karren M
authors.initials: KM
authors.lastname: Plain
authors.affiliation: Faculty of Veterinary Science, The University of Sydney, 425 Werombi Road, Camden 2570, NSW, Australia.
authors.forename: Kumudika
authors.initials: K
authors.lastname: de Silva
authors.affiliation: Faculty of Veterinary Science, The University of Sydney, 425 Werombi Road, Camden 2570, NSW, Australia.
authors.forename: Douglas
authors.initials: D
authors.lastname: Begg
authors.affiliation: Faculty of Veterinary Science, The University of Sydney, 425 Werombi Road, Camden 2570, NSW, Australia.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Whittington
authors.affiliation: Faculty of Veterinary Science, The University of Sydney, 425 Werombi Road, Camden 2570, NSW, Australia. Electronic address: auriol.purdie@sydney.edu.au.
authors.forename: Auriol C
authors.initials: AC
authors.lastname: Purdie
mesh_terms: D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000209:etiology / Q000235:genetics* / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D015870:Gene Expression; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology / Q000502:physiology; D007371:Interferon-gamma / Q000096:biosynthesis; D050356:Lipid Metabolism / Q000235:genetics*; D008954:Models, Biological; D016927:Mycobacterium avium subsp. paratuberculosis / Q000276:immunology / Q000472:pathogenicity; D020411:Oligonucleotide Array Sequence Analysis; D010283:Paratuberculosis / Q000209:etiology / Q000235:genetics* / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D007371:Interferon-gamma; D002784:Cholesterol
keywords: 24 DHCR; CD38; Ca(+); GIMAP; GNLY; Johne's disease; LDLR; Mycobacterium avium subsp. paratuberculosis; SCD-1; cholesterol