InterPro is an integrated resource for protein families, domains and functional sites, which integrates the following protein signature databases: PROSITE, PRINTS, ProDom, Pfam, SMART, TIGRFAMs, PIRSF, SUPERFAMILY, Gene3D and PANTHER. The latter two new member databases have been integrated since the last publication in this journal. There have been several new developments in InterPro, including an additional reading field, new database links, extensions to the web interface and additional match XML files. InterPro has always provided matches to UniProtKB proteins on the website and in the match XML file on the FTP site. Additional matches to proteins in UniParc (UniProt archive) are now available for download in the new match XML files only. The latest InterPro release (13.0) contains more than 13 000 entries, covering over 78% of all proteins in UniProtKB. The database is available for text- and sequence-based searches via a webserver (), and for download by anonymous FTP (). The InterProScan search tool is now also available via a web service at .

Blood fluke proteases play pivotal roles in the processes of invasion, nutrition acquisition, immune evasion, and other host-parasite interactions. Hundreds of genes encoding putative proteases have been identified in the recently published schistosome genomes. However, the expression profiles of these proteases in Schistosoma species have not yet been systematically analyzed. We retrieved and culled the redundant protease sequences of Schistosoma japonicum, Schistosoma mansoni, Echinococcus multilocularis, and Clonorchis sinensis from public databases utilizing bioinformatic approaches. The degradomes of the four parasitic organisms and Homo sapiens were then comparatively analyzed. A total of 262 S. japonicum protease sequences were obtained and the expression profiles generated using whole-genome microarray. Four main clusters of protease genes with different expression patterns were identified: proteases up-regulated in hepatic schistosomula and adult worms, egg-specific or predominantly expressed proteases, cercaria-specific or predominantly expressed proteases, and constantly expressed proteases. A subset of protease genes with different expression patterns were further validated using real-time quantitative PCR. The present study represents the most comprehensive analysis of a degradome in Schistosoma species to date. These results provide a firm foundation for future research on the specific function(s) of individual proteases and may help to refine anti-proteolytic strategies in blood flukes.

BackgroundSchistosoma japonicum is a pathogen of the phylum Platyhelminthes that causes zoonotic schistosomiasis in China and Southeast Asian countries where a lack of efficient measures has hampered disease control. The development of tools for diagnosis of acute and chronic infection and for novel antiparasite reagents relies on understanding the biological mechanisms that the parasite exploits.ResultsIn this study, the polyadenylated transcripts from the male and female S. japonicum were sequenced using a high-throughput RNA-seq technique. Bioinformatic and experimental analyses focused on post-transcriptional RNA processing, which revealed extensive alternative splicing events in the adult stage of the parasite. The numbers of protein-coding sequences identified in the transcriptomes of the female and male S. japonicum were 15,939 and 19,501 respectively, which is more than predicted from the annotated genome sequence. Further, we identified four types of post-transcriptional processing, or alternative splicing, in both female and male worms of S. japonicum: exon skipping, intron retention, and alternative donor and acceptor sites. Unlike mammalian organisms, in S. japonicum, the alternative donor and acceptor sites were more common than the other two types of post-transcriptional processing. In total, respectively 13,438 and 16,507 alternative splicing events were predicted in the transcriptomes of female and male S. japonicum.ConclusionsBy using RNA-seq technology, we obtained the global transcriptomes of male and female S. japonicum. These results further provide a comprehensive view of the global transcriptome of S. japonicum. The findings of a substantial level of alternative splicing events dynamically occurring in S. japonicum parasitization of mammalian hosts suggest complicated transcriptional and post-transcriptional regulation mechanisms employed by the parasite. These data should not only significantly improve the re-annotation of the genome sequences but also should provide new information about the biology of the parasite.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-715) contains supplementary material, which is available to authorized users.

BackgroundSchistosomiasis is one of the most widely distributed parasitic diseases in the world. Schistosoma japonicum, a zoonotic parasite with a wide range of mammalian hosts, is one of the major pathogens of this disease. Although numerous studies on schistosomiasis japonica have been performed using laboratory animal models, systematic comparative analysis of whole-genome expression profiles in parasites from different laboratory animals and nature mammalian hosts is lacking to date.Methodology/Principal FindingsAdult schistosomes were obtained from laboratory animals BALB/c mice, C57BL/6 mice, New Zealand white rabbits and the natural host, water buffaloes. The gene expression profiles of schistosomes from these animals were obtained and compared by genome-wide oligonucleotide microarray analysis. The results revealed that the gene expression profiles of schistosomes from different laboratory animals and buffaloes were highly consistent (r>0.98) genome-wide. Meanwhile, a total of 450 genes were identified to be differentially expressed in schistosomes which can be clustered into six groups. Pathway analysis revealed that these genes were mainly involved in multiple signal transduction pathways, amino acid, energy, nucleotide and lipid metabolism. We also identified a group of 1,540 abundantly and stably expressed gene products in adult worms, including a panel of 179 Schistosoma- or Platyhelminthes-specific genes that may be essential for parasitism and may be regarded as novel potential anti-parasite intervention targets for future research.Conclusions/SignificanceThis study provides a comprehensive database of gene expression profiles of schistosomes derived from different laboratory animals and water buffaloes. An expanded number of genes potentially affecting the development of schistosomes in different animals were identified. These findings lay the foundation for schistosomiasis research in different laboratory animals and natural hosts at the transcriptional level and provide a valuable resource for screening anti-schistosomal intervention targets.

bT cell immunoglobulin-and mucin-domain-containing molecule 3 (Tim-3) has been regarded as an important regulatory factor in both adaptive and innate immunity. Recently, Tim-3 was reported to be involved in Th2-biased immune responses in mice infected with Schistosoma japonicum, but the exact mechanism behind the involvement of Tim-3 remains unknown. The present study aims to understand the role of Tim-3 in the immune response against S. japonicum infection. Tim-3 expression was determined by flow cytometry, and increased Tim-3 expression was observed on CD4 ؉ and CD8 ؉ T cells, NK1.1 ؉ cells, and CD11b؉ cells from the livers of S. japonicum-infected mice. However, the increased level of Tim-3 was lower in the spleen than in the liver, and no increase in Tim-3 expression was observed on splenic CD8؉ T cells or CD11b Schistosomiasis is a human helminth infection that is estimated to afflict 200 million people worldwide (1). The pathogenesis of schistosomiasis is caused by egg-induced granuloma formation and subsequent fibrosis in hepatic and intestinal tissues, which is believed to be caused by the acquisition and accumulation of immune cells in the affected organs. The immune response that occurs during this process is complicated and poorly understood. During the early stages of infection, a type 1 T-helper-cell (Th1) response is induced by parasite migration and adult worms. As the eggs are released from the mature adult worms, the response is then polarized into a Th2 response 4 to 6 weeks after the initial infection. This is then followed by the development of granulomas around the eggs trapped in the liver. Macrophages surround the deposited eggs and play a pivotal role in the formation of fibrosis (2), since these cells are involved in Th2 development during schistosomiasis (3) and undergo either M1 or M2 activation (4-6). M2 macrophages are essential for host protection via the production of interleukin-10 (IL-10) but simultaneously promote progressive pathology due to granuloma formation (7,8). Although the pathogenesis of schistosomal infection has long been known, the molecules and cells involved in immune triggering against the parasite remain enigmatic.T cell immunoglobulin-and mucin-domain-containing molecule 3 (Tim-3) is an important regulatory factor in both adaptive and innate immunity (9). Tim-3 is preferentially expressed on activated Th1 cells but not Th2 cells (10). After binding to its ligand galectin-9, Tim-3 induces the death of Th1 cells and negatively regulates the Th1 response (11-13). This process plays critical roles in autoimmunity, allergy, viral infection, and transplant tolerance (9). Increased Tim-3 also leads to CD8 ϩ T cell exhaustion, thereby abrogating proliferation, cytotoxicity, and cytokine production during viral infection (14, 15) and acute graft-versushost disease (16). Apart from T cells, Tim-3 is also expressed on a variety of other immune cells, such as natural killer (NK) cells, monocytes, macrophages, and mast cells (17-19). Tim-3 was reported to inhibit NK cell c...