Identification of the Schistosoma mansoni TNF-Alpha Receptor Gene and the Effect of Human TNF-Alpha on the Parasite Gene Expression Profile |
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Authors: | Katia C. Oliveira Mariana L. P. Carvalho Thiago M. Venancio Patricia A. Miyasato Toshie Kawano Ricardo DeMarco Sergio Verjovski-Almeida |
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Affiliation: | 1. Laboratory of Gene Expression in Eukaryotes, Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil.; 2. Laboratory of Parasitology, Instituto Butantan, São Paulo, Brazil.; 3. Departamento de Física e Informática, Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos, Brazil.;Uniformed Services University, United States of America |
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Abstract: | BackgroundSchistosoma mansoni is the major causative agent of schistosomiasis. The parasite takes advantage of host signals to complete its development in the human body. Tumor necrosis factor-alpha (TNF-α) is a human cytokine involved in skin inflammatory responses, and although its effect on the adult parasite''s metabolism and egg-laying process has been previously described, a comprehensive assessment of the TNF-α pathway and its downstream molecular effects is lacking.Methodology/Principal FindingsIn the present work we describe a possible TNF-α receptor (TNFR) homolog gene in S. mansoni (SmTNFR). SmTNFR encodes a complete receptor sequence composed of 599 amino acids, and contains four cysteine-rich domains as described for TNFR members. Real-time RT-PCR experiments revealed that SmTNFR highest expression level is in cercariae, 3.5 (±0.7) times higher than in adult worms. Downstream members of the known human TNF-α pathway were identified by an in silico analysis, revealing a possible TNF-α signaling pathway in the parasite. In order to simulate parasite''s exposure to human cytokine during penetration of the skin, schistosomula were exposed to human TNF-α just 3 h after cercariae-to-schistosomula in vitro transformation, and large-scale gene expression measurements were performed with microarrays. A total of 548 genes with significantly altered expression were detected, when compared to control parasites. In addition, treatment of adult worms with TNF-α caused a significantly altered expression of 1857 genes. Interestingly, the set of genes altered in adults is different from that of schistosomula, with 58 genes in common, representing 3% of altered genes in adults and 11% in 3 h-old early schistosomula.Conclusions/SignificanceWe describe the possible molecular elements and targets involved in human TNF-α effect on S. mansoni, highlighting the mechanism by which recently transformed schistosomula may sense and respond to this host mediator at the site of cercarial penetration into the skin. |
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