Unknown,Transcriptomics,Genomics,Proteomics

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Transcriptional Responses of Schistosoma japonicum Exposed in vivo to Sub-Lethal Dosages of Praziquantel

ABSTRACT: We have used a Schistosoma japonicum infected murine model with in vivo sub-lethal dosages of praziquantel against adult parasites. Differential gene expression of parasites was followed between 30 minutes and 24 hours post- drug administration, using a whole transcriptome microarray platform. Differential gene expression was considered separately between parasite gender. Total RNA was isolated from adult (7 week post cercarial challenge) Schistosoma japonicum male and females. Gene expression was determined through hybridisation on an Agilent custom designed oligo microarray.

ORGANISM(S): Schistosoma japonicum

SUBMITTER: Geoffrey Gobert

PROVIDER: E-GEOD-41149 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Alternatively activated macrophages (AAMφs) play important roles in a number of Th2 driven pathologies including asthma and allergy, and a number of parasitic infections. Our studies, and those of others, investigating the pathologies associated with infection with the helminth Schistosoma japonicum implicate a role for AAMφs in fibrosis and immunomodulation.. In the present study we show that S. japonicum-secreted egg antigens are able to induce the alternative activation of macrophages as characterised by the induction of Chi3l3 and Arg1 expression. Retnla, another common marker of AAMφs, was not consistently induced in these macrophages suggesting that the specific function of these cells may differ to those induced by S. mansoni and other parasites. Closer examination of the gene expression profile and functionality of these cells identified pathways independent of Retnla expression that could be important for their immunomodulatory activity such as modulating expression of T-cell co-stimulatory molecules and chemokines. In vivo generated S. japonicum soluble egg antigen stimulated AAMφs also exhibited a reduction in their phagocytic ability likely related to the induction of IL4 and decreased expression of cell surface receptors. Additionally these macrophages exhibited reduced expression of Toll-like receptors (TLRs) and an associated reduction in responsiveness to stimulation with TLR ligands. We did not observe pathways that would suggest that AAMφs have a direct profibrotic activity. Taken together, these data describe a mechanism by which alternative activation of macrophages may be induced during S. japonicum infection and highlight the importance of the context of activation in directing AAMφ phenotype and function. The gene expression profile of Schistosoma japonicum soluble egg antigen (SEA)-stimulated macrophages was compared with that of PBS stimulated controls. Macrophages were isolated from the peritoneal cavity of BALB/c mice (n=6 per group) stimulated by intraperitoneal injection with SEA or PBS. The macrophages were pooled and RNA was extracted from these cells. Microarray analysis was performed on cRNA synthesised from total RNA derived from these macrophages. The experiment was performed twice creating two biological replicates. Fold-change (relative to the respective PBS control) reported in supplementary file linked below.

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Transcriptional Responses of Schistosoma japonicum Exposed in vivo to Sub-Lethal Dosages of Praziquantel

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