The effect of PrP(Sc) accumulation on inflammatory gene expression within sheep peripheral lymphoid tissue.

Accumulation of the misfolded prion protein, PrP(Sc) in the central nervous system (CNS) is strongly linked to progressive neurodegenerative disease. For many transmissible spongiform encephalopathies (TSEs), peripheral lymphoid tissue is an important site of PrP(Sc) amplification but without gross immunological consequence. Susceptible VRQ homozygous New Zealand Cheviot sheep were infected with SSBP/1 scrapie by inoculation in the drainage area of the prescapular lymph nodes.

Transcriptome analysis of CNS immediately before and after the detection of PrP(Sc) in SSBP/1 sheep scrapie.

Sheep scrapie is a transmissible spongiform encephalopathy (TSE), progressive and fatal neurodegenerative diseases of the central nervous system (CNS) linked to the accumulation of misfolded prion protein, PrP(Sc). New Zealand Cheviot sheep, homozygous for the VRQ genotype of the PRNP gene are most susceptible with an incubation period of 193 days with SSBP/1 scrapie. However, the earliest time point that PrP(Sc) can be detected in the CNS is 125 days (D125).

The immunology and genetics of resistance of sheep to Teladorsagia circumcincta.

Teladorsagia circumcincta is one of the most economically important gastrointestinal nematode parasites of sheep in cool temperate regions, to which sheep show genetically-varying resistance to infection. This is a very common parasite and viable sheep production requires the extensive use of anthelmintic drugs. However, the emergence of drug-resistant parasites has stimulated the search for alternative control strategies to curb production losses.

Expression of sheep interleukin 23 (IL23A, alpha subunit p19) in two distinct gastrointestinal diseases.

This paper reports the sequence of sheep interleukin 23A (p19), and shows that it shares 98% identity with bovine IL23A, 85% with human and 76% with mouse IL23A. It also reports the existence of two allelic variants that differ largely within the region encoding the amino terminal polypeptide signal sequence. An optimized RT-qPCR assay was used to quantify IL23A transcripts in sheep infected with two common gastrointestinal pathogens, the intracellular bacterium Mycobacterium avium subspecies paratuberculosis and the parasitic nematode Teladorsagia circumcincta.

Relationship between susceptibility of Blackface sheep to Teladorsagia circumcincta infection and an inflammatory mucosal T cell response.

Teladorsagia circumcincta is the most economically important gastrointestinal (abomasal) nematode parasite of sheep in cool temperate regions, to which sheep show genetically-varying resistance to infection. Lambs, from parents with genetic variation for resistance, were trickle infected with L3 larvae over 12 weeks. 45 lambs were identified with a range of susceptibilities as assessed by: adult worm count at post mortem, faecal egg count (FEC) and IgA antibody levels.

Gene expression analysis in distinct regions of the central nervous system during the development of SSBP/1 sheep scrapie.

Rodent scrapie models have been exploited to define the molecular basis for the progression of neuropathological changes in TSE diseases. We aim to assess whether CNS gene expression changes consistently observed in mouse models are of generic relevance, for example to natural TSE diseases, or are TSE strain, host species or brain region specific. Six genes, representing distinct physiological pathways and showing consistent changes in expression levels with disease progression in murine scrapie models were analysed for expression (RT-qPCR) in defined regions of the sheep brain at various times after SSBP/1 scrapie infection.

Differential expression of pattern recognition receptors during the development of foetal sheep.

Pattern recognition receptors (PRRs) play a crucial role in the initiation of the adaptive immune response. Immunological competence of foetal lambs occurs progressively throughout gestation, and in order to understand the role played by PRRs in foetal immunological competence, we quantified transcript expression, in the skin and spleen, of the TLRs, key C-type lectins and CARD15 during the critical second trimester. These data show that lambs express the same spectrum of PRRs as the adult but that the level of expression for most is dependent on developmental age.

Differential expression of pattern recognition receptors in sheep tissues and leukocyte subsets.

The various members of the different pattern recognition receptor families are now recognized as playing a crucial role in the initial interactions between a pathogen and the host. This paper identifies all 10 members of the TLR family in sheep as well as key members of the C-type lectin and NLR families. Our data show that sheep possess the 'human' and not the 'mouse' pattern of TLRs and confirm the high degree of sequence identity between orthologous genes in the different species.