title: The influence of trematode parasite burden on gene expression in a mammalian host.
abstract: Parasites can profoundly impact their hosts and are responsible for a plethora of debilitating diseases. To identify global changes in host gene expression related to parasite infection, we sequenced, assembled, and annotated the liver transcriptomes of Balb/cj mice infected with the trematode parasite Schistosoma mansoni and compared the results to uninfected mice. We used two different methodologies (i.e. de novo and reference guided) to evaluate the influence of parasite sequences on host transcriptome assembly.
  
  
  
  Our results demonstrate that the choice of assembly methodology significantly impacted the proportion of parasitic reads detected from the host library, yet the presence of non-target (xenobiotic) sequences did not create significant structural errors in the assembly. After removing parasite sequences from the mouse transcriptomes, we analyzed host gene expression under different parasite infection levels and observed significant differences in the associated immunologic and metabolic responses based on infection level. In particular, genes associated with T-helper type 1 (Th-1) and T-helper type 2 (Th-2) were up-regulated in infected mice whereas genes related to amino acid and carbohydrate metabolism were down-regulated in infected mice. These changes in gene expression scale with infection status and likely impact the evolutionary fitness of hosts.
  
  
  
  Overall, our data indicate that a) infected mice reduce the expression of key metabolic genes in direct proportion to their infection level; b) infected mice similarly increase the expression of key immune genes in response to infection; c) patterns of gene expression correspond to the pathological symptoms of schistosomiasis; and d) identifying and filtering out non-target sequences (xenobiotics) improves differential expression prediction. Our findings identify parasite targets for RNAi or other therapies and provide a better understanding of the pathology and host immune repertoire involved in response to S. mansoni infections.
authors: Department of Biological Sciences, Purdue University, West Lafayette, Indiana, 47907, USA. bhagya.wijayawardena@gmail.com.
authors: Bhagya K
authors: BK
authors: Wijayawardena
authors: Department of Biological Sciences, Purdue University, West Lafayette, Indiana, 47907, USA.
authors: Dennis J
authors: DJ
authors: Minchella
authors: Department of Biological Sciences, Purdue University, West Lafayette, Indiana, 47907, USA.|Departments of Biological Sciences, Forestry and Natural Resources, Purdue University, West Lafayette, Indiana, 47907, USA.
authors: J Andrew
authors: JA
authors: DeWoody
mesh_terms: D000596:Amino Acids / Q000096:biosynthesis / Q000276:immunology; D000818:Animals; D050260:Carbohydrate Metabolism / Q000235:genetics / Q000276:immunology; D058487:Cercaria / Q000472:pathogenicity* / Q000502:physiology; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D015723:Gene Library; D006790:Host-Parasite Interactions; D007113:Immunity, Innate; D008099:Liver / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D059208:Parasite Load; D012550:Schistosoma mansoni / Q000472:pathogenicity* / Q000502:physiology; D012555:Schistosomiasis mansoni / Q000235:genetics* / Q000276:immunology / Q000469:parasitology; D015398:Signal Transduction; D012908:Snails / Q000469:parasitology; D018417:Th1 Cells / Q000276:immunology / Q000469:parasitology; D058408:Th1-Th2 Balance; D018418:Th2 Cells / Q000276:immunology / Q000469:parasitology; D059467:Transcriptome / Q000276:immunology*
chemical_list: D000596:Amino Acids
keywords: Differential expression; Illumina HiSeq; Immune response; Non-target sequences; RNAseq; Schistosoma mansoni; Xenobiotics