title: Novel gene expression responses in the ovine abomasal mucosa to infection with the gastric nematode Teladorsagia circumcincta.
abstract: Infection of sheep with the gastric nematode Teladorsagia circumcincta results in distinct Th2-type changes in the mucosa, including mucous neck cell and mast cell hyperplasia, eosinophilia, recruitment of IgA/IgE producing cells and neutrophils, altered T-cell subsets and mucosal hypertrophy. To address the protective mechanisms generated in animals on previous exposure to this parasite, gene expression profiling was carried out using samples of abomasal mucosa collected pre- and post- challenge from animals of differing immune status, using an experimental model of T. circumcincta infection. Recently developed ovine cDNA arrays were used to compare the abomasal responses of sheep immunised by trickle infection with worm-naïve sheep, following a single oral challenge of 50 000 T. circumcincta L3. Key changes were validated using qRT-PCR techniques. Immune animals demonstrated highly significant increases in levels of transcripts normally associated with cytotoxicity such as granulysin and granzymes A, B and H, as well as mucous-cell derived transcripts, predominantly calcium-activated chloride channel 1 (CLCA1). Challenge infection also induced up-regulation of transcripts potentially involved in initiating or modulating the immune response, such as heat shock proteins, complement factors and the chemokine CCL2. In contrast, there was marked infection-associated down-regulation of gene expression of members of the gastric lysozyme family. The changes in gene expression levels described here may reflect roles in direct anti-parasitic effects, immuno-modulation or tissue repair.
authors.affiliation: The Roslin Institute and R(D)SVS, University of Edinburgh, Roslin, Midlothian, EH25 9RG, Scotland, UK. pamaknight@gmail.com.
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Knight
authors.forename: Susan E
authors.initials: SE
authors.lastname: Griffith
authors.forename: Alan D
authors.initials: AD
authors.lastname: Pemberton
authors.forename: Judith M
authors.initials: JM
authors.lastname: Pate
authors.forename: Lauren
authors.initials: L
authors.lastname: Guarneri
authors.forename: Katherine
authors.initials: K
authors.lastname: Anderson
authors.forename: Richard T
authors.initials: RT
authors.lastname: Talbot
authors.forename: Sarah
authors.initials: S
authors.lastname: Smith
authors.forename: David
authors.initials: D
authors.lastname: Waddington
authors.forename: Mark
authors.initials: M
authors.lastname: Fell
authors.forename: Alan L
authors.initials: AL
authors.lastname: Archibald
authors.forename: Stewart T G
authors.initials: ST
authors.lastname: Burgess
authors.forename: David W
authors.initials: DW
authors.lastname: Smith
authors.forename: Hugh R P
authors.initials: HR
authors.lastname: Miller
authors.forename: Ivan W
authors.initials: IW
authors.lastname: Morrison
mesh_terms: D000018:Abomasum / Q000378:metabolism* / Q000469:parasitology; D000818:Animals; D020224:Expressed Sequence Tags; D020869:Gene Expression Profiling / Q000662:veterinary; D005786:Gene Expression Regulation; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000469:parasitology; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis / Q000662:veterinary; D016133:Polymerase Chain Reaction / Q000662:veterinary; D017422:Sequence Analysis, DNA / Q000662:veterinary; D012756:Sheep; D012757:Sheep Diseases / Q000235:genetics* / Q000276:immunology / Q000469:parasitology; D014251:Trichostrongyloidea / Q000502:physiology*; D014252:Trichostrongyloidiasis / Q000276:immunology / Q000378:metabolism / Q000469:parasitology / Q000662:veterinary*