Differential release and phagocytosis of tegument glycoconjugates in neurocysticercosis: implications for immune evasion strategies.
Differential release and phagocytosis of tegument glycoconjugates in neurocysticercosis: implications for immune evasion strategies.
复制标题
神经囊肿中的Tegument糖缀合物的差异释放和吞噬作用：对免疫逃避策略的影响。
DOI：
10.1371/journal.pntd.0000218
复制
发表时间：
2008-04-09
影响因子：
3.8
通讯作者：
Teale JM
中科院分区：
文献类型：
--
作者：
Alvarez JI;Rivera J;Teale JM
神经囊虫病（NCC）是一种中枢神经系统（CNS）感染的蠕虫带绦虫（带绦虫）。症状的严重程度与免疫反应的强度有关。首先，有一段很长的无症状期，宿主免疫似乎无法解决感染，随后是慢性超敏反应。由于对这种感染的初始反应知之甚少，因此采用了使用cestode Mesocestoides corti （syn. Mesocestoides vogae）的小鼠模型来分析寄生虫感染早期的形态学变化。结果发现，与神经组织密切接触的被皮释放出corti物质。用体外标记的寄生虫感染小鼠中枢神经系统证实了这些结果。由于超过95%的NCC患者对基于碳水化合物的抗原表现出体液反应，并且已知被膜富含糖缀合物（GCs），因此分析了这些类型分子在人类，猪和小鼠NCC标本中的表达。采用荧光染料标记的酰肼和荧光染料标记的对不同碳水化合物具有特异性的凝集素来测定被皮中存在的gc。所有使用的凝集素都标记在被皮上。与异集素b4结合的GCs在感染的第一天就脱落，并且不会被寄生虫重新合成，而与小麦胚芽凝集素和concavalinA结合的GCs在整个感染过程中不断释放。与这三种凝集素结合的GCs被宿主细胞吸收。相比之下，花生凝集素结合GCs留在寄生虫上，而在宿主细胞中未检测到。利用抗T. solium和M. corti的抗体证实了宿主细胞中发现的凝集素结合GCs的寄生来源。我们认为，被囊gc的快速和持续释放在众所周知的蠕虫免疫调节作用中起着关键作用，包括免疫逃避和许多NCC患者的终身炎症后遗症。神经囊虫病（NCC）是一种由优先迁移到大脑的绦虫寄生虫幼虫引起的疾病。它的特点是长时间无症状，这被认为是由寄生虫逃避宿主免疫的能力造成的。迄今为止，在症状出现之前宿主-寄生虫相互作用的机制仍然未知。在这项研究中，我们通过多种免疫荧光技术评估感染的不同阶段，利用与人类观察到的疾病过程非常相似的小鼠模型。我们发现，寄生虫分泌的分子阵列根据所研究的感染阶段而变化。在感染的早期，寄生虫会永久地释放出独特的分子，从而在大脑中迅速扎根。随着感染的发生，不同分子的持续释放似乎通过下调参与其识别和破坏的分子来促进寄生虫的持续存在。当寄生虫在药物治疗后死亡时，这些分子的丢失可能解释了患者突然的炎症反应。这些分子的表征将导致我们对寄生虫使用的复杂免疫调节机制的理解取得进展，并为治疗策略提供新的方法。
Neurocysticercosis (NCC) is an infection of the central nervous system (CNS) by the metacestode of the helminth Taenia solium. The severity of the symptoms is associated with the intensity of the immune response. First, there is a long asymptomatic period where host immunity seems incapable of resolving the infection, followed by a chronic hypersensitivity reaction. Since little is known about the initial response to this infection, a murine model using the cestode Mesocestoides corti (syn. Mesocestoides vogae) was employed to analyze morphological changes in the parasite early in the infection. It was found that M. corti material is released from the tegument making close contact with the nervous tissue. These results were confirmed by infecting murine CNS with ex vivo–labeled parasites. Because more than 95% of NCC patients exhibit humoral responses against carbohydrate-based antigens, and the tegument is known to be rich in glycoconjugates (GCs), the expression of these types of molecules was analyzed in human, porcine, and murine NCC specimens. To determine the GCs present in the tegument, fluorochrome-labeled hydrazides as well as fluorochrome-labeled lectins with specificity to different carbohydrates were used. All the lectins utilized labeled the tegument. GCs bound by isolectinB4 were shed in the first days of infection and not resynthesized by the parasite, whereas GCs bound by wheat germ agglutinin and concavalinA were continuously released throughout the infectious process. GCs bound by these three lectins were taken up by host cells. Peanut lectin-binding GCs, in contrast, remained on the parasite and were not detected in host cells. The parasitic origin of the lectin-binding GCs found in host cells was confirmed using antibodies against T. solium and M. corti. We propose that both the rapid and persistent release of tegumental GCs plays a key role in the well-known immunomodulatory effects of helminths, including immune evasion and life-long inflammatory sequelae seen in many NCC patients. Neurocysticercosis (NCC) is a disease caused by the larval form of a tapeworm parasite that preferentially migrates to the brain. It is characterized by a long asymptomatic period thought to result from the parasite's ability to evade host immunity. To date, the mechanisms of host–parasite interaction before symptoms develop remain unknown. In this study we evaluate by multiple immunofluorescent techniques distinct stages of the infection, making use of a murine model that closely resembles the disease process observed in humans. We discovered that the array of molecules secreted by the parasite varies according to the phase of infection studied. Early in infection, the parasite permanently sheds distinct molecules, allowing a rapid establishment in the brain. As the infection ensues, the continuous release of different molecules appears to facilitate the persistence of the parasite by downregulating molecules involved in its recognition and destruction. Loss of such molecules when the parasite dies after drug treatment may explain sudden inflammatory responses in patients. Characterization of these molecules will lead to advances in our understanding of the complex immunoregulatory mechanisms used by parasites and to new approaches for therapeutic strategies.