title: Toll-like receptor genes are differentially expressed at the sites of infection during the progression of Johne's disease in outbred sheep.
abstract: Toll-like receptors (TLR) are engaged by ligands on microbial pathogens to initiate innate and adaptive immune responses. Little is known about TLR involvement during infection with Mycobacterium avium subsp. paratuberculosis (M. ptb), the cause of Johne's disease in ruminants, although there is a profound immunopathological response in affected animals. We have analyzed the expression of 10 TLR genes relative to validated reference genes at predilection sites in ileum, jejunum and associated lymph nodes as well as in peripheral blood, to determine if TLR expression is altered in response to infection with M. ptb in outbred sheep. Previously unexposed animals from two flocks and animals from three naturally infected flocks were used with restricted maximum likelihood linear mixed modeling applied to determine significant differences. These were related to the pathologies observed at different stages of infection in exposed sheep, after allowing for other sources of variation. In most cases there were differences in TLR expression between early paucibacillary and multibacillary groups when compared to uninfected sheep, with most TLRs for the paucibacillary group having lower expression levels than the multibacillary group. Increased expression of TLR1-5, and 8 was observed in ileum or jejunum, and TLR1-4, 6, and 8 in mesenteric lymph nodes. There was a trend for increased expression of TLR1, 2, and 6-8 in PBMCs of exposed compared to non-exposed animals. Further study of TLR expression in Johne's disease in ruminants is warranted as these observed differences may help explain pathogenesis and may be useful in the future diagnosis of M. ptb infection.
authors.affiliation: Faculty of Veterinary Science, University of Sydney, PMB3, Camden, NSW 2570, Australia.
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Taylor
authors.forename: Ling
authors.initials: L
authors.lastname: Zhong
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Begg
authors.forename: Kumudika
authors.initials: K
authors.lastname: de Silva
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Whittington
mesh_terms: D000818:Animals; D018450:Disease Progression; D005786:Gene Expression Regulation; D006651:Histocytochemistry / Q000662:veterinary; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D007082:Ileum / Q000276:immunology / Q000382:microbiology; D007583:Jejunum / Q000276:immunology / Q000382:microbiology; D016014:Linear Models; D008198:Lymph Nodes / Q000276:immunology / Q000382:microbiology; D016927:Mycobacterium avium subsp. paratuberculosis / Q000276:immunology*; D010283:Paratuberculosis / Q000235:genetics* / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary; D012756:Sheep; D012757:Sheep Diseases / Q000235:genetics* / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051193:Toll-Like Receptors / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology
chemical_list: D051193:Toll-Like Receptors