Schistosome Syntenin Partially Protects Vaccinated Mice against Schistosoma mansoni Infection

被引:11
|
作者
Figueiredo, Barbara C. [1 ,2 ,3 ]
Assis, Natan R. G. [1 ,2 ]
Morais, Suellen B. [1 ,2 ]
Ricci, Natasha D. [1 ,2 ]
Pinheiro, Carina S. [1 ,2 ,4 ]
Martins, Vicente P. [1 ,2 ,5 ]
Bicalho, Rodrigo M. [1 ,2 ]
Da'dara, Akram A. [3 ]
Skelly, Patrick J. [3 ]
Oliveira, Sergio C. [1 ,2 ]
机构
[1] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Bioquim & Imunol, Belo Horizonte, MG, Brazil
[2] CNPq MCT, INCT DT, Salvador, BA, Brazil
[3] Tufts Univ, Cummings Sch Vet Med, Dept Infect Dis & Global Hlth, North Grafton, MA USA
[4] Univ Fed Bahia, Dept Biointeracao, Inst Ciencias Saude, Salvador, BA, Brazil
[5] Univ Brasilia, Inst Ciencias Biol, Dept Biol Celular, Brasilia, DF, Brazil
来源
PLOS NEGLECTED TROPICAL DISEASES | 2014年 / 8卷 / 08期
关键词
IFN-GAMMA; HELMINTH DISEASES; INDUCE PROTECTION; TEGUMENT PROTEIN; IMMUNE-RESPONSE; RESEARCH AGENDA; PDZ PROTEIN; CELL; EXPRESSION; IMMUNIZATION;
D O I
10.1371/journal.pntd.0003107
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
Background: Schistosomiasis is a neglected tropical disease caused by several species of trematode of the genus Schistosoma. The disease affects more than 200 million people in the world and causes up to 280,000 deaths per year, besides having high morbidity due to chronic illness that damages internal organs. Current schistosomiasis control strategies are mainly based on chemotherapy, but many researchers believe that the best long-term strategy to control disease is a combination of drug treatment and immunization with an anti-schistosome vaccine. Among the most promising molecules as vaccine candidates are the proteins present in the tegument and digestive tract of the parasite. Methodology/Principal Findings: In this study, we describe for the first time Schistosoma mansoni syntenin (SmSynt) and we evaluate its potential as a recombinant vaccine. We demonstrate by real-time PCR that syntenin is mainly expressed in intravascular life stages (schistosomula and adult worms) of the parasite life cycle and, by confocal microscopy, we localize it in digestive epithelia in adult worms and schistosomula. Administration of siRNAs targeting SmSynt leads to the knockdown of syntenin gene and protein levels, but this has no demonstrable impact on parasite morphology or viability, suggesting that high SmSynt gene expression is not essential for the parasites in vitro. Mice immunization with rSmSynt, formulated with Freund's adjuvant, induces a Th1-type response, as suggested by the production of IFN-gamma and TNF-alpha by rSmSynt-stimulated cultured splenocytes. The protective effect conferred by vaccination with rSmSynt was demonstrated by 30-37% reduction of worm burden, 38-43% reduction in the number, and 35-37% reduction in the area, of liver granulomas. Conclusions/Significance: Our report is the first characterization of syntenin in Schistosoma mansoni and our data suggest that this protein is a potential candidate for the development of a multi-antigen vaccine to control schistosomiasis.
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页数:13
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