Unknown,Transcriptomics,Genomics,Proteomics

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A differential polarization of Th1, Th2 and Treg immune response determines resistance and susceptibility of sheep breeds to Teladorsagia circumcincta infection

ABSTRACT: Gastrointestinal nematode (GIN) is a major economic and health concern is sheep farming. Sheep breeds such as Texel are relatively resistant to GIN than the Suffolk. With the objective to understand the underlying genetic mechanism of resistance and susceptibility at the transcriptomic level, two groups of animal from both the breed were artificially (orally) infected with 30,000 L3 larvae of prominent GIN Teladorsagia circumcincta. Subgroups of animals from each breed were slaughtered on day 0, 3, 7, 14 and 21 of post infection (p.i.). Transcriptomic profiling of abomasal lymph node was performed using RNA-seq. The perturbations in gene expression profiles in both the breeds were evident and Texel showed a more tightly regulated immune response than the Suffolk. The number of differentially expressed (DE) genes between the breeds was highest (437) on un-infected control (day 0) and lowest (173) on day 7 p.i.. Pathway analysis of DE genes identified 3 significant pathways, which involved only more highly expressed genes of Suffolk breed on day 0 and only more highly expressed genes of Texel (with one exception) on day 7 p.i.. The Th1, Th2 and Treg response was evident in response to GIN in Texel and was synchronized, while in Suffolk Th1 response was reduced after infection and pronounced Th2 and Treg was not evident. The study suggests maximum level of transcriptional activity in both breeds on day 7 p.i. and there was a shift of transcriptional activity from Suffolk on day 0 to Texel on day 7 p.i.. Suffolk had a reduced Th1 response with less pronounced Th2 and Treg immune response, while Texel had an active and synchronized Th1/Th2/Treg immune response in response to GIN infection. Abomasal lymph node tissue was taken from control (n=10) and experimentally infected (with T. circumcincta) lambs (n=36) from Texel and Suffolk breed on day 0, 3, 7, 14 and 21 post infection.

ORGANISM(S): Ovis aries

SUBMITTER: Albin Ahmed

PROVIDER: E-GEOD-43241 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Fetal cartilage fully regenerates following injury while in adult mammals cartilage injury leads to osteoarthritis (OA). OA is characterized by cartilage breakdown and joint inflammation and associated with significant pain and socioeconomic costs. As no clinically satisfactory treatment is available to date, disease-modifying therapies aimed to achieve cartilage regeneration are urgently required. The inherent regeneration potential of fetal individuals may hold answers to this unmet need. Therefore, to characterize the differences in fetal and adult response to cartilage injury, we carried out histology and comprehensive proteome analyses on fetal (day 80/150-day gestation) and adult cartilage samples one (fetal samples) and three (adult and fetal samples) days after surgical induction of a full-thickness cartilage lesion. In addition, proteins secreted by inflamed fetal MSCs in vitro were compared with the in vivo response to injury to evaluate their therapeutic potential. Histology of synovial samples revealed the presence of neutrophils one day post injury (p.i.) and an influx of macrophages into the subsynovial tissue on day 3 p.i. in fetal samples. In contrast, adult synovial samples showed invasion of neutrophils on day 3 p.i. Activation and migration of Iba1+- macrophages of the synovial lining was observed both in fetal and adult animals. Comparative mass spectrometry revealed 57 proteins significantly up-regulated (> 2FC, FDR<0.05), and 67 proteins significantly down-regulated (<-2 FC) upon injury in adults. Neutrophil-related proteins and acute phase proteins were the two major upregulated protein groups in adult cartilage following injury compared to fetal sheep. In contrast, several immunomodulating proteins and growth factors were significantly higher expressed in the fetus than the adult. Comparison of the in vitro MSCs with the in vivo fetal proteome revealed shared upregulation of 17 proteins, which were considered to be of potential therapeutic interest. The results of this study support our molecular understanding of successful fetal cartilage healing and new therapeutic strategies to induce regeneration in adult articular cartilage by modulating the inflammatory environment. The shared protein upregulation in fetal cartilage in vivo and in fetal MSCS during in vitro inflammation supports the possible therapeutic potential of these factors in specific and fetal MSCs in general.

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A differential polarization of Th1, Th2 and Treg immune response determines resistance and susceptibility of sheep breeds to Teladorsagia circumcincta infection

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