Human IgG1 Responses to Surface Localised Schistosoma mansoni Ly6 Family Members Drop following Praziquantel Treatment.
Human IgG1 Responses to Surface Localised Schistosoma mansoni Ly6 Family Members Drop following Praziquantel Treatment.
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DOI：
10.1371/journal.pntd.0003920
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发表时间：
2015
影响因子：
3.8
通讯作者：
Hoffmann KF
中科院分区：
文献类型：
--
作者：
Chalmers IW;Fitzsimmons CM;Brown M;Pierrot C;Jones FM;Wawrzyniak JM;Fernandez-Fuentes N;Tukahebwa EM;Dunne DW;Khalife J;Hoffmann KF
被七胺盐覆盖的合体被是一种重要的解剖学适应，使血吸虫寄生虫能够在确定的宿主体内保持长期的血管内驻留。研究这一表层中存在的蛋白质及其在感染过程中所引发的免疫反应对于我们理解宿主/寄生虫的相互作用至关重要。最近的研究发现了许多新的被膜表面蛋白，包括三个含有uPAR/Ly6结构域的蛋白(SmCD59a、SmCD59b和Sm29)(在本研究中更名为SmLy6A、SmLy6B和SmLy6D)。虽然SmLy6A(SmCD59a)和SmLy6D(Sm29)疫苗在实验模型中诱导保护性免疫，但人类免疫球蛋白对具有代表性的SmLy6家族成员的反应仍未得到深入研究。通过基于PSI-BLAST的搜索，我们对曼氏血吸虫Ly6家族(SmLy6A-K)进行了全面的重新分析。我们的研究将成员数量扩大到11个(包括3个新蛋白)，并提供了强有力的证据，表明先前确定的候选疫苗Sm29(更名为SmLy6D)是一个独特的包含双uPAR/Ly6结构域的代表。典型的半胱氨酸残基、信号肽和GPI锚点的存在强烈表明所有的SmLy6蛋白都是与细胞表面结合的。为了提供证据证明SmLy6成员在人类群体中具有免疫原性，我们报告了在吡喹酮治疗前后感染曼氏葡萄球菌的乌干达男性队列中针对两个表面结合代表(SmLy6A和SmLy6B)的IgG1(以及IgG4和IgE)反应。虽然治疗前SmLy6A和SmLy6B的IgG1流行率在研究人群中不同(分别占队列的7.4%和25.3%)，但这两个值都高于表面下被膜抗原SmTAL1的IgG1流行率(2.7%)。此外，治疗后对表面相关的SmLy6A和SmLy6B的免疫球蛋白1水平显著下降(分别为p=0.020和p<；0.001)，而对亚表面SmTAL1的免疫球蛋白1水平上升。总的来说，这些结果扩大了在曼氏血吸虫中发现的SmLy6蛋白的数量，并特别证明了在流行社区感染期间，表面相关的SmLy6A和SmLy6B激发了免疫反应。成虫可以在人体血液中存活数年，而不会受到宿主免疫反应的不利影响。确定寄生虫表面的哪些蛋白质，并了解它们如何促进宿主/寄生虫的长期关系，是开发新的干预策略的关键步骤。在这里，利用一种全面的生物信息学方法来鉴定曼氏血吸虫具有不同表面相关特征的基因产物，包括信号肽、疏水C末端、二硫键和uPAR/Ly6结构域，我们鉴定了11种感兴趣的蛋白质。令人放心的是，这些蛋白质包括与血吸虫表面相关的三个代表(这里称为SmLy6A、SmLy6B和SmLy6D)以及三个新成员(SmLy6G、SmLy6H和SmLy6J)。为了确定表面相关的SmLy6成员是否被曼氏血吸虫感染者识别，我们在一个地方性人群中专门检查了对SmLy6A和SmLy6B的抗体反应。我们的工作扩大了推测的血吸虫细胞表面相关蛋白的数量，并提供了对流行社区中针对两个代表的抗体反应的动态的更好的理解。
The heptalaminate-covered, syncytial tegument is an important anatomical adaptation that enables schistosome parasites to maintain long-term, intravascular residence in definitive hosts. Investigation of the proteins present in this surface layer and the immune responses elicited by them during infection is crucial to our understanding of host/parasite interactions. Recent studies have revealed a number of novel tegumental surface proteins including three (SmCD59a, SmCD59b and Sm29) containing uPAR/Ly6 domains (renamed SmLy6A SmLy6B and SmLy6D in this study). While vaccination with SmLy6A (SmCD59a) and SmLy6D (Sm29) induces protective immunity in experimental models, human immunoglobulin responses to representative SmLy6 family members have yet to be thoroughly explored. Using a PSI-BLAST-based search, we present a comprehensive reanalysis of the Schistosoma mansoni Ly6 family (SmLy6A-K). Our examination extends the number of members to eleven (including three novel proteins) and provides strong evidence that the previously identified vaccine candidate Sm29 (renamed SmLy6D) is a unique double uPAR/Ly6 domain-containing representative. Presence of canonical cysteine residues, signal peptides and GPI-anchor sites strongly suggest that all SmLy6 proteins are cell surface-bound. To provide evidence that SmLy6 members are immunogenic in human populations, we report IgG1 (as well as IgG4 and IgE) responses against two surface-bound representatives (SmLy6A and SmLy6B) within a cohort of S. mansoni-infected Ugandan males before and after praziquantel treatment. While pre-treatment IgG1 prevalence for SmLy6A and SmLy6B differs amongst the studied population (7.4% and 25.3% of the cohort, respectively), these values are both higher than IgG1 prevalence (2.7%) for a sub-surface tegumental antigen, SmTAL1. Further, post-treatment IgG1 levels against surface-associated SmLy6A and SmLy6B significantly drop (p = 0.020 and p < 0.001, respectively) when compared to rising IgG1 levels against sub-surface SmTAL1. Collectively, these results expand the number of SmLy6 proteins found within S. mansoni and specifically demonstrate that surface-associated SmLy6A and SmLy6B elicit immunological responses during infection in endemic communities. Adult schistosome parasites can live in the human bloodstream for years without being adversely affected by the host immune response. Identifying which proteins are on the surface of the parasite and understanding how they contribute to long-term host/parasite relationships is an essential step in developing novel intervention strategies. Here, utilising a comprehensive bioinformatics approach to identify Schistosoma mansoni gene products sharing distinct surface-associated features including signal peptides, hydrophobic C-termini, disulfide bonds and uPAR/Ly6 domains, we identified eleven proteins of interest. These proteins, reassuringly, include three representatives previously found associated with the schistosome surface (here termed SmLy6A, SmLy6B and SmLy6D) as well as three novel members (SmLy6G, SmLy6H and SmLy6J). To identify if surface-associated SmLy6 members are recognized by S. mansoni infected individuals, we specifically examined antibody responses to SmLy6A and SmLy6B in an endemic human population. Our work expands the number of putative cell surface associated schistosome proteins and provides a greater understanding of the dynamics of antibody responses in endemic communities against two representatives.
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影响因子：
9.4
作者：
AURIAULT, C;GRASMASSE, H;CAPRON, A
通讯作者：
CAPRON, A
影响因子：
2
作者：
Farias, Leonardo P.;Tararam, Cibele A.;de Cerqueira Leite, Luciana Cezar
通讯作者：
de Cerqueira Leite, Luciana Cezar
影响因子：
2.8
作者：
Bergquist, NR
通讯作者：
Bergquist, NR
影响因子：
3.8
作者：
Farias LP;Krautz-Peterson G;Tararam CA;Araujo-Montoya BO;Fraga TR;Rofatto HK;Silva FP Jr;Isaac L;Da'dara AA;Wilson RA;Shoemaker CB;Leite LC
通讯作者：
Leite LC
影响因子：
3.8
作者：
Cardoso FC;Macedo GC;Gava E;Kitten GT;Mati VL;de Melo AL;Caliari MV;Almeida GT;Venancio TM;Verjovski-Almeida S;Oliveira SC
通讯作者：
Oliveira SC