Project description:Inflammatory immune disorders such as inflammatory bowel disease (IBD) and multiple sclerosis (MS) are major health problems. Currently, the intestinal whipworm Trichuris suis is being explored in clinical trials to reduce inflammation in these diseases, however, the mechanisms by which the parasite affects the host immune system are not known. Here we determined the effects of T. suis soluble products (SPs) on toll-like receptor-4 (TLR4)-stimulated human dendritic cells (DCs) using Illumina bead chip gene arrays. Pathway analysis of lipopolysaccharide (LPS)-stimulated DCs with or without T. suis treatment showed that costimulation with T. suis SPs resulted in a down-regulation of both the myeloid differentiation primary response gene 88 (MyD88)-dependent and the TIR-domain-containing adaptor-inducing interferon-β (TRIF)-dependent signalling pathways triggered by TLR4. These data were verified using quantitative real-time PCR of several key genes within these pathways and/or defining their protein levels. In addition, T. suis SPs induce Rab7b, a negative regulator of TLR4 signalling that interferes with its trafficking, which coincided with a reduced surface expression of TLR4. These data indicate that the mechanism by which T. suis SPs reduce inflammatory responses is through suppression of both TLR4 signalling and surface expression on DCs.
Project description:We describe the transcriptional changes occurring in lamina propria mononuclear cells (LPMC) and intestinal epithelial cells (IEC) upon Trichuris suis ova (TSO) treatment in a rabbit model of DSS colitis
Project description:Trichuris muris is very closely related to the human parasite T. trichiura sharing cross reactive antigens. Moreover, it is a remarkably tractable model system for dissecting immune responses and host parasite relationships and is actively being investigated in a number of laboratories worldwide. T. muris is a naturally occurring nematode parasite of mice which resides in the caecum and colon and has a direct oral faecal life cycle. High-throughput sequencing of Trichuris muris transcriptome for de novo assembly of transcripts. The main objective of this project is to recognize genes expressed in given life stages. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/
