Abstract
Schistosomes are the causative agents of schistosomiasis, one of the most prevalent and serious of the parasitic diseases that currently infects ∼200 million people worldwide. Schistosome excretory/secretory (ES) proteins have been shown to play important roles in modulating mammalian host immune systems. In our current study, we performed a global proteomics identification of the ES proteins from adult worms of Schistosoma japonicum, one of the three major schistosome species. Our results unambiguously identified 101 proteins, including 53 putatively secreted proteins. By quantitative analysis, we revealed fatty acid-binding protein as a major constituent of the in vitro ES proteome. Strikingly the heat shock proteins HSP70s, HSP90, and HSP97 constituted the largest protein family in the ES proteome, implying a central role for these proteins in immunomodulation in the host-parasite relationship. Other important S. japonicum ES proteins included actins, 14-3-3, aminopeptidase, enolase, and glyceraldehyde-3-phosphate dehydrogenase, some of which have been considered as viable vaccine candidates and therapeutic targets. A comparison with previous studies suggests that 48.5% of S. japonicum ES proteins are common to other parasite ES products, indicating that the molecular mechanisms involved in evading the host immune response may be conserved across different parasites. Interestingly seven host proteins, including antimicrobial protein CAP18, immunoglobulins, and a complement component, were identified among in vitro S. japonicum ES products likely originating from the schistosome tegument or gut, indicating that host innate and acquired immune systems could defend against schistosome invasion. Our present study represents the first attempt at profiling S. japonicum ES proteins, provides an insight into host-parasite interactions, and establishes a resource for the development of diagnostic agents and vaccines for the control of schistosomiasis.
Footnotes
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↵* This work was supported by Chinese National Key Program on Basic Research (973) Grants 2007CB513100 and 2006CB708510, Chinese High-Tech Research and Development Program (863) Grants 2006AA02Z318 and 2007AA02Z153, the National Foundation for Excellence Doctoral Project, Shanghai Commission for Science and Technology Grants 06JC14059 and 05DZ22201, the China Postdoctoral Science Foundation, and Shanghai Rising-Star Program Grant 07QA14043.
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The on-line version of this article (available at http://www.mcponline.org) contains supplemental material.
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↵2 M. Berriman, unpublished data.
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↵3 Z. Chen, unpublished data.
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↵4 S.-Y. Wang, unpublished data.
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↵1 The abbreviations used are:
- ES
- excretory/secretory
- CAP
- cytoskeleton-associated protein
- DB
- database
- ESP
- ES product
- EST
- expressed sequence tag
- FABP
- fatty acid-binding protein
- FPR
- false-positive rate
- GAPDH
- glyceraldehyde-3-phosphate dehydrogenase
- HSP
- heat shock protein
- Ig
- immunoglobulin
- nano-LC-MS/MS
- nanoscale capillary LC-MS/MS
- NC
- non-classical
- RP
- reverse-phase
- SC
- spectral count
- SCX
- strong cation exchange
- SOD
- superoxide dismutase
- SP
- signal peptide
- TPX
- thioredoxin peroxidase
- WCL
- whole cell lysis
- BLAST
- basic local alignment search tool
- Mowse
- molecular weight search
- Sj
- S. japonicum
- Sm
- S. mansoni
- MSD
- mass selective detector
- XCT
- X-ray computed tomography.
- Received November 24, 2008.
- Accepted March 11, 2009.
- © 2009 by The American Society for Biochemistry and Molecular Biology, Inc.