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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

The Schistosome Esophagus Is a `Hotspot' for Microexon and Lysosomal Hydrolase Gene Expression: Implications for Blood Processing

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Autor(es):
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Wilson, R. Alan [1] ; Li, Xiao Hong [1, 2] ; MacDonald, Sandy [3] ; Neves, Leandro Xavier [4] ; Vitoriano-Souza, Juliana [5] ; Leite, Luciana C. C. [5] ; Farias, Leonardo P. [5, 6] ; James, Sally [3] ; Ashton, Peter D. [3] ; DeMarco, Ricardo [7] ; Borges, William Castro [4]
Número total de Autores: 11
Afiliação do(s) autor(es):
[1] Univ York, Dept Biol, Ctr Immunol & Infect, York YO10 5DD, N Yorkshire - England
[2] Natl Inst Parasit Dis, Chinese Ctr Dis Control & Prevent, Shanghai - Peoples R China
[3] Univ York, Dept Biol, Genom & Bioinformat Lab, York YO10 5DD, N Yorkshire - England
[4] Univ Fed Ouro Preto, Dept Ciencias Biol, Ouro Preto, MG - Brazil
[5] Inst Butantan, Ctr Biotecnol, Sao Paulo - Brazil
[6] Fundacao Oswaldo Cruz FIOCRUZ, Ctr Pesquisa Goncalo Moniz, Salvador, BA - Brazil
[7] Univ Sao Paulo, Inst Fis Sao Carlos, BR-13560 Sao Carlos, SP - Brazil
Número total de Afiliações: 7
Tipo de documento: Artigo Científico
Fonte: PLoS Neglected Tropical Diseases; v. 9, n. 12 DEC 2015.
Citações Web of Science: 17
Resumo

Background The schistosome esophagus is divided into anterior and posterior compartments, each surrounded by a dense cluster of gland cell bodies, the source of distinct secretory vesicles discharged into the lumen to initiate the processing of ingested blood. Erythrocytes are lysed in the lumen, leucocytes are tethered and killed and platelets are eliminated. We know little about the proteins secreted from the two glands that mediate these biological processes. Methodology/Principal Findings We have used subtractive RNA-Seq to characterise the complement of genes that are differentially expressed in a head preparation, compared to matched tissues from worm tails. The expression site of representative highlighted genes was then validated using whole munt in situ hybridisation (WISH). Mapping of transcript reads to the S. mansoni genome assembly using Cufflinks identified similar to 90 genes that were differentially expressed >fourfold in the head preparation; similar to 50 novel transcripts were also identified by de novo assembly using Trinity. The largest subset (27) of secreted proteins was encoded by microexon genes (MEGs), the most intense focus identified to date. Expression of three (MEGs 12, 16, 17) was confirmed in the anterior gland and five (MEGs 8.1, 9, 11, 15 and 22) in the posterior gland. The other major subset comprised nine lysosomal hydrolases (aspartyl proteases, phospholipases and palmitoyl thioesterase), again localised to the glands. Conclusions A proportion of the MEG-encoded secretory proteins can be classified by their primary structure. We have suggested testable hypotheses about how they might function, in conjunction with the lysosomal hydrolases, to mediate the biological processes that occur in the esophagus lumen. Antibodies bind to the esophageal secretions in both permissive and self-curing hosts, suggesting that the proteins represent a novel panel of untested vaccine candidates. A second major task is to identify which of them can serve as immune targets. (AU)

Processo FAPESP: 14/09361-9 - Estudo dos genes de micro-exon (MEGs) do parasita humano Schistosoma mansoni e da interação de seus produtos protéicos com células humanas
Beneficiário:Ricardo de Marco
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 12/23124-4 - Investigação dos mecanismos efetores da vacina atenuada de Schistosoma mansoni utilizando Systems Vaccinology
Beneficiário:Luciana Cezar de Cerqueira Leite
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 12/18095-5 - Analisando os mecanismos efetores nos pólos Th1/Th2 da vacina de cercária atenuada de Schistosoma mansoni utilizando Biologia Sistêmica: "Systems Vaccinology"
Beneficiário:Juliana Vitoriano de Souza
Linha de fomento: Bolsas no Brasil - Pós-Doutorado