Evidence That Rhesus Macaques Self-Cure from a Schistosoma japonicum Infection by Disrupting Worm Esophageal Function: A New Route to an Effective Vaccine?
Evidence That Rhesus Macaques Self-Cure from a Schistosoma japonicum Infection by Disrupting Worm Esophageal Function: A New Route to an Effective Vaccine?
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恒河猴通过破坏蠕虫食道功能来自愈日本血吸虫感染的证据：有效疫苗的新途径？
DOI：
10.1371/journal.pntd.0003925
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发表时间：
2015
影响因子：
3.8
通讯作者：
Wilson RA
中科院分区：
文献类型：
--
作者：
Li XH;Xu YX;Vance G;Wang Y;Lv LB;van Dam GJ;Cao JP;Wilson RA
恒河猴是一种特殊的宿主，它能从已建立的感染中自我治愈，此后对攻击表现出牢固的免疫力，是疫苗开发的理想模型。此前，自我治愈的免疫学基础得到了证实;存活的蠕虫已经停止进食，但免疫压力如何实现这一点尚不清楚。食道不仅是血液的通道，而且在血液的处理过程中起着核心作用。前、后食道腺分泌物与流入的血液混合，导致红细胞溶解，束缚和杀死白细胞。方法/主要发现我们分析了感染日本血吸虫的恒河猴的自愈过程。粪便卵排出量和循环抗原水平用于绘制成熟蠕虫种群的建立及其随后的死亡。灌注时存活雌性动物的生理应激从其苍白、萎缩的外观中尤其明显，而在两种性别动物中均观察到食管结构和功能的变化。在前部区域的电子显微镜下发现，囊泡分泌过程被破坏，衬里皱纹的尖端被大大扩大的囊泡和囊泡释放的假定位点被IgG的强烈沉积物所掩盖。饥饿蠕虫的后食管腔被细胞碎片堵塞，内衬细胞质板紧密粘附，也可能阻止分泌。后腺分泌的七种蛋白质被鉴定，并检测到其中一些或全部的IgG反应。在冷冻切片上，内源性恒河猴IgG与分泌的SjMEG 4.1、8.2、9、11和瓦尔-7共定位，表明它们是破坏功能的潜在靶标。结论/意义我们的数据表明，恒河猴自我治愈阻断食管功能与抗体的腺体的蛋白质产物提供了一类新的潜在的疫苗靶点。
Background Rhesus macaques are unusual among schistosome hosts, self-curing from an established infection and thereafter manifesting solid immunity against a challenge, an ideal model for vaccine development. Previously, the immunological basis of self-cure was confirmed; surviving worms had ceased feeding but how immunological pressure achieved this was unclear. The schistosome esophagus is not simply a conduit for blood but plays a central role in its processing. Secretions from the anterior and posterior esophageal glands mix with incoming blood causing erythrocyte lysis and tethering and killing of leucocytes. Methodology/Principal Findings We have analysed the self-cure process in rhesus macaques infected with Schistosoma japonicum. Faecal egg output and circulating antigen levels were used to chart the establishment of a mature worm population and its subsequent demise. The physiological stress of surviving females at perfusion was especially evident from their pale, shrunken appearance, while changes in the structure and function of the esophagus were observed in both sexes. In the anterior region electron microscopy revealed that the vesicle secretory process was disrupted, the tips of lining corrugations being swollen by greatly enlarged vesicles and the putative sites of vesicle release obscured by intense deposits of IgG. The lumen of the posterior esophagus in starving worms was occluded by cellular debris and the lining cytoplasmic plates were closely adherent, also potentially preventing secretion. Seven proteins secreted by the posterior gland were identified and IgG responses were detected to some or all of them. Intrinsic rhesus IgG colocalized with secreted SjMEGs 4.1, 8.2, 9, 11 and VAL-7 on cryosections, suggesting they are potential targets for disruption of function. Conclusions/Significance Our data suggest that rhesus macaques self-cure by blocking esophagus function with antibody; the protein products of the glands provide a new class of potential vaccine targets.
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影响因子：
3.8
作者：
Li XH;de Castro-Borges W;Parker-Manuel S;Vance GM;Demarco R;Neves LX;Evans GJ;Wilson RA
通讯作者：
Wilson RA
影响因子：
3.2
作者：
Li XH;Stark M;Vance GM;Cao JP;Wilson RA
通讯作者：
Wilson RA
影响因子：
4
作者：
Messenger, Scott W.;Falkowski, Michelle A.;Groblewski, Guy E.
通讯作者：
Groblewski, Guy E.
影响因子：
9.4
作者：
Corstjens, Paul L. A. M.;van Lieshout, Lisette;van Dam, Govert J.
通讯作者：
van Dam, Govert J.
影响因子：
2.4
作者：
Mair, GR;Maule, AG;Halton, DW
通讯作者：
Halton, DW