Unknown,Transcriptomics,Genomics,Proteomics

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Alternatively activated mononuclear phagocytes from the skin site of infection and the impact of IL-4RÎ± signaling on CD4+T cell survival in draining lymph nodes after repeated exposure to Schistosoma mansoni cercariae

ABSTRACT: In areas endemic for schistosomiasis, repeated exposure to infective cercariae is a frequent occurrence, and repeated exposure of murine skin to Schistosoma mansoni resulted in CD4+ T cells becoming hypo-responsive. Here potential contributory mechanisms were investigated. In the skin infection site, three mononuclear phagocyte populations were identified (tissue macrophages, dendritic cells, and macrophages) which exhibited up-regulation of genes associated with alternative activation, in particular the gene encoding RELMÎ±. However, in repeatedly infected mice deficient in RELMÎ±, there was no change in the abundance of mononuclear phagocytes in the skin, and CD4+ cells in the skin draining lymph nodes remained hypo-responsive. In mice deficient for IL-4RÎ±, required for alternative activation, levels of dermal regulatory IL-10 were reduced and there was an increase in the abundance of antigen presenting MHC-IIhigh cells, which was accompanied by increased numbers of CD4+ T cells. Although the absence of IL-4RÎ± did not translate into increased CD4+ cell responsiveness, they exhibited lower expression of Fas/FasL, resulting in decreased apoptosis/cell death and increased cell viability. This study highlights a mechanism through which IL-4RÎ± may regulate the immune system through the induction of IL-10 and regulation of Fas/FasL mediated cell death. Mice were infected 1x or 4x with S. mansoni cercariae via the pinnae. Pinnae were harvested 4 days after the final infection and the DEC obtained after an overnight culture in vitro. Cells were then stained with F4/80 APC and MHC-II PE and four different populations sorted (using the MoFlo or the Astrios) based on their expression profiles. Several mice (12-18) from each group were pooled to generate each replicate.

ORGANISM(S): Mus musculus

SUBMITTER: David Sanin

PROVIDER: E-GEOD-81938 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Protein variation in blood-dwelling schistosome worms generated by differential splicing of micro-exon gene transcripts. The infective schistosome cercaria develops from an undifferentiated germ ball within the daughter sporocyst in the molluscan host, during which considerable morphological development and synthesis of proteins essential for infection occurs. The free-living, non-feeding cercaria is notable for its swimming and host location behaviour. On contact with host skin it rapidly penetrates, replaces its tegument surface membranes, and begins body remodelling, before crossing the dermis to exit the skin via a blood vessel. Such a ‘violent’ transition from snail to fresh water to mammalian host should be accompanied by remarkable changes in the patterns of gene expression. All gene models from version E of the S. mansoni genome (www.GeneDB.org) were incorporated into a 350K feature Roche-NimbleGen, high-density oligonucleotide array. From a map-ordered list, every 13th 50mer was chosen as a probe. Double-stranded cDNA from three biological replicates each of germ balls, cercariae, and day 3 schistosomula was hybridised to the array without amplification. Statistical analysis was carried out using programmes from the Bioconductor suite (Gentleman et al. 2004 Genome Biol 5(10):R80). More than 1000 loci were shown to be differentially expressed in each of the comparisons between the three life cycle stages. Gene ontology (GO) analysis was then carried out to discover the categories enriched in each stage. In addition custom categories based on biological function (e.g. stress response) or parasite tissue (e.g. tegument) were analysed. Three biological replicates each of germ balls, cercariae, day 3 in vitro cultured schistosomula, and eggs were used. No technical replicates were included. This is the first genome-wide microarray platform for S. mansoni. It was used to investigate the gene expression patterns of the above lifecycle stages. The first three are the stages before, during and after penetration of mammalian host skin.

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Alternatively activated mononuclear phagocytes from the skin site of infection and the impact of IL-4RÎ± signaling on CD4+T cell survival in draining lymph nodes after repeated exposure to Schistosoma mansoni cercariae

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