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

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Wilson, R. Alan ; Li, Xiao Hong ; MacDonald, Sandy ; Neves, Leandro Xavier ; Vitoriano-Souza, Juliana ; Leite, Luciana C. C. ; Farias, Leonardo P. ; James, Sally ; Ashton, Peter D. ; DeMarco, Ricardo ; Borges, William Castro

• Tipo de documento: Artigo Científico
• Fonte: PLoS Neglected Tropical Diseases; v. 9, n. 12, p. 25-pg., 2015-12-01.

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: 12/23124-4 - Investigação dos mecanismos efetores da vacina atenuada de Schistosoma mansoni utilizando Systems Vaccinology
• Beneficiário: Luciana Cezar de Cerqueira Leite
• Modalidade de apoio: 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
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• 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
• Modalidade de apoio: Auxílio à Pesquisa - Regular