Taenia crassiceps

  • 文章类型: Journal Article
    几十年来,头带虫已被用作研究人类和猪囊虫病的实验模型。即使,它的生命周期,组织组织,在宿主中引起的超微结构和免疫反应,已经被广泛描述,还有许多其他生物学问题有待解决。在本研究中,我们重新审视了两种最常用菌株(WFU和ORF)中囊尾蚴的肌肉和神经结构,使用常规染色和共聚焦显微镜成像,旨在组装更新的解剖结构。两种菌株之间的差异,包括幼芽幼虫发育过程中的极化过程,强调。我们还进行了与其他相关扁虫中的肽能神经过程相关的基因搜索。这些发现可以帮助了解两种菌株中存在或不存在的解剖和分子后果。
    Taenia crassiceps has been used for decades as an experimental model for the study of human and porcine cysticercosis. Even though, its life cycle, tissue organization, ultrastructure and immune response elicited in the host, have been extensively described, there are many other biological questions remaining to be addressed. In the present study we revisited the muscle and neural architecture of cysticerci in two of the most frequently used strains (WFU and ORF), using conventional staining and confocal microscopy imaging, aiming to assemble an updated anatomy. Differences between both strains, including polarization processes during development of the young budding larvae, are emphasized. We also performed a search for genes that have been related to peptidergic neural processes in other related flatworms. These findings can help to understand the anatomical and molecular consequences of the scolex presence or absence in both strains.
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  • 文章类型: Journal Article
    扁虫以其非凡的再生能力而闻名,一种依赖于全能细胞的细胞,称为c虫中的发芽细胞。羟基脲(HU)耗尽发芽细胞会影响寄生虫的再生。这里,我们通过体外试验研究了HU处理(25mM和40mMHU持续6天)后,囊尾股癣中发芽细胞的减少和恢复。评价活力和形态变化。在第3天和第6天评估囊尾蚴的活动性和形态恢复,治疗6天后。使用EdU评估增殖细胞的数量。我们的结果显示了大小的形态变化,形状,和40mM剂量下消失的囊尾蚴的数量。两种浓度的HU处理6天后,囊尾蚴的迁移率较低。在25mMHU处理后恢复的第3天和第6天,观察到增殖细胞的部分恢复。蛋白质组学和基因本体论分析确定了与DNA结合相关的蛋白质组中的修饰,DNA损伤,糖酵解酶,细胞骨架,骨骼肌,和RNA结合。
    Flatworms are known for their remarkable regenerative ability, one which depends on totipotent cells known as germinative cells in cestodes. Depletion of germinative cells with hydroxyurea (HU) affects the regeneration of the parasite. Here, we studied the reduction and recovery of germinative cells in T. crassiceps cysticerci after HU treatment (25 mM and 40 mM of HU for 6 days) through in vitro assays. Viability and morphological changes were evaluated. The recovery of cysticerci\'s mobility and morphology was evaluated at 3 and 6 days, after 6 days of treatment. The number of proliferative cells was evaluated using EdU. Our results show morphological changes in the size, shape, and number of evaginated cysticerci at the 40 mM dose. The mobility of cysticerci was lower after 6 days of HU treatment at both concentrations. On days 3 and 6 of recovery after 25 mM of HU treatment, a partial recovery of the proliferative cells was observed. Proteomic and Gene Ontology analyses identified modifications in protein groups related to DNA binding, DNA damage, glycolytic enzymes, cytoskeleton, skeletal muscle, and RNA binding.
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  • 文章类型: Journal Article
    过氧化物酶(Prxs)和谷胱甘肽过氧化物酶(GPxs)是硫醇依赖性抗氧化系统的主要酶,负责减少宿主生物通过有氧代谢或寄生生物产生的H2O2。这些抗氧化剂系统在细胞中维持适当的氧化还原状态。the虫的囊尾蚴能耐受这种氧化剂的毫摩尔浓度。要了解Prxs在此节食中所起的作用,Prxs的两个基因,在猪带虫(TsPrx1和TsPrx3)的基因组中鉴定,被克隆。蛋白质的序列表明两种同种型都属于典型的Prxs2-Cys类别。此外,TsPrx3具有一个线粒体定位信号肽和两个与过度氧化相关的基序(-GGLG-和-YP-)。我们的动力学表征将它们指定为硫氧还蛋白过氧化物酶(TPxs)。虽然TsPrx1和TsPrx3表现出相同的催化效率,来自T.crassiceps的硫氧还蛋白-谷胱甘肽还原酶(TcTGR)分别高出五倍和八倍。此外,与TsPrx1和TsPrx3相比,后者对H2O2的亲和力较低(>30倍)。TcTGR在其C端含有Sec残基,这赋予了额外的过氧化物酶活性。上述方面意味着TsPrx1和TsPrx3在低H2O2浓度下具有催化活性,并且TcTGR在高H2O2浓度下起作用。这些结果可以解释为什么囊尾股虫可以耐受高H2O2浓度。
    Peroxiredoxins (Prxs) and glutathione peroxidases (GPxs) are the main enzymes of the thiol-dependent antioxidant systems responsible for reducing the H2O2 produced via aerobic metabolism or parasitic organisms by the host organism. These antioxidant systems maintain a proper redox state in cells. The cysticerci of Taenia crassiceps tolerate millimolar concentrations of this oxidant. To understand the role played by Prxs in this cestode, two genes for Prxs, identified in the genome of Taenia solium (TsPrx1 and TsPrx3), were cloned. The sequence of the proteins suggests that both isoforms belong to the class of typical Prxs 2-Cys. In addition, TsPrx3 harbors a mitochondrial localization signal peptide and two motifs (-GGLG- and -YP-) associated with overoxidation. Our kinetic characterization assigns them as thioredoxin peroxidases (TPxs). While TsPrx1 and TsPrx3 exhibit the same catalytic efficiency, thioredoxin-glutathione reductase from T. crassiceps (TcTGR) was five and eight times higher. Additionally, the latter demonstrated a lower affinity (>30-fold) for H2O2 in comparison with TsPrx1 and TsPrx3. The TcTGR contains a Sec residue in its C-terminal, which confers additional peroxidase activity. The aforementioned aspect implies that TsPrx1 and TsPrx3 are catalytically active at low H2O2 concentrations, and the TcTGR acts at high H2O2 concentrations. These results may explain why the T. crassiceps cysticerci can tolerate high H2O2 concentrations.
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  • 文章类型: Journal Article
    结直肠癌(CRC)是全球最常见的致命性肿瘤之一。尽管努力改善CRC的早期诊断,患者死亡率仍近50%。CRC的主要治疗策略是手术,可能伴有化疗和放疗。所用的常规和一线化疗剂是5-氟尿嘧啶(5FU)。然而,效率低。用亚叶酸和奥沙利铂或伊立替康联合治疗可提高5FU治疗的有效性。不幸的是,大多数患者会产生耐药性,导致疾病进展。这里,我们评估了潜在的替代辅助治疗5FU的效果,蠕虫衍生的棘齿带虫(TcES)分子,关于治疗晚期结肠炎相关结肠癌。TcES的使用通过下调免疫调节细胞因子的表达来增强5FU对已建立的结肠肿瘤的作用,Il-10和Tgf-β,和促炎细胞因子,Tnf-α和Il-17a,并降低与恶性肿瘤相关的分子标志物水平,cyclinD1和Ki67均参与细胞凋亡抑制和β-catenin信号通路。TcES+5FU治疗促进NK细胞募集和颗粒酶B1在肿瘤部位的释放,从而诱导肿瘤细胞死亡。此外,它恢复了与Mdm2表达降低相关的P53活性。对人结肠癌细胞系的体外分析显示,用TcES+5FU治疗通过调节P53和P21信号传导途径显著降低细胞增殖和迁移。我们的发现表明,第一次在体内,蠕虫来源的排泄/分泌产物可能会增强5FU对已建立的结肠肿瘤的作用。
    Colorectal cancer (CRC) is one of the most prevalent fatal neoplasias worldwide. Despite efforts to improve the early diagnosis of CRC, the mortality rate of patients is still nearly 50%. The primary treatment strategy for CRC is surgery, which may be accompanied by chemotherapy and radiotherapy. The conventional and first-line chemotherapeutic agent utilized is 5-fluorouracil (5FU). However, it has low efficiency. Combination treatment with leucovorin and oxaliplatin or irinotecan improves the effectiveness of 5FU therapy. Unfortunately, most patients develop drug resistance, leading to disease progression. Here, we evaluated the effect of a potential alternative adjuvant treatment for 5FU, helminth-derived Taenia crassiceps (TcES) molecules, on treating advanced colitis-associated colon cancer. The use of TcES enhanced the effects of 5FU on established colonic tumors by downregulating the expression of the immunoregulatory cytokines, Il-10 and Tgf-β, and proinflammatory cytokines, Tnf-α and Il-17a, and reducing the levels of molecular markers associated with malignancy, cyclin D1, and Ki67, both involved in apoptosis inhibition and the signaling pathway of β-catenin. TcES+5FU therapy promoted NK cell recruitment and the release of Granzyme B1 at the tumor site, consequently inducing tumor cell death. Additionally, it restored P53 activity which relates to decreased Mdm2 expression. In vitro assays with human colon cancer cell lines showed that therapy with TcES+5FU significantly reduced cell proliferation and migration by modulating the P53 and P21 signaling pathways. Our findings demonstrate, for the first time in vivo, that helminth-derived excreted/secreted products may potentiate the effect of 5FU on established colon tumors.
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  • 文章类型: Journal Article
    为了确定IL-4/IL13受体在交替激活的巨噬细胞(AAM或M2)的发育中的作用,以及它们在调节对蠕虫寄生虫的肠外阶段的免疫力中的作用,我们追踪了缺乏IL-4Rα基因的小鼠品系(IL-4Rα-/-)和巨噬细胞/中性粒细胞特异性IL-4Rα缺陷型小鼠品系(LysMcreIL-4Rα-/lox或cre/LoxP)的感染.而100%的T.crassiceps感染的IL-4Rα/(WT)小鼠携带大量寄生虫,超过50%的eIL-4Rα-/-小鼠解决了感染。大约88%的LysMcreIL-4Rα-/lox小鼠表现出对感染的灭菌免疫。其余几只受感染的cre/LoxP小鼠在其腹膜腔中显示出最低数量的幼虫。WT小鼠无法控制感染与抗原特异性Th2型反应相关,具有较高水平的IgG1,IL-4,IL-13和总IgE,减少NO产生,和增加的精氨酸酶活性。相比之下,IL-4Rα-/-半抗性小鼠显示Th1/Th2组合应答。此外,来自WT小鼠的巨噬细胞显示出更高的精氨酸酶-1和RELM-α转录本,以及与抗CD3/CD28刺激的T细胞相比具有强大抑制活性的PD-L2的表达增加;所有这些特征都与AAM或M2巨噬细胞表型相关。相比之下,IL-4Rα-/-和LysMcreIL-4Rα-/lox小鼠均未完全发展AAM或显示对CD3/CD28刺激的T细胞的抑制活性,减少PDL2表达。此外,T-CD8+但无T-CD4+细胞显示抑制表型,在WT和IL-4Rα-/-中Tim-3和PD1表达增加,在T.crassiceps感染的LysMcreIL-4Rα-/lox小鼠中不存在。这些发现证明了IL-4信号通路在囊虫病期间维持AAM及其抑制活性中的关键作用。提示AAM在有利于T.crusiceps感染的易感性中的关键作用。因此,这些抑制细胞的缺失是成功控制实验性囊虫病的主要机制之一。
    To determine the role that the IL-4/IL13 receptor plays in the development of alternatively activated macrophages (AAM or M2) and their role in the regulation of immunity to the extraintestinal phase of the helminth parasite Taenia crassiceps, we followed the infection in a mouse strain lacking the IL-4Rα gene (IL-4Rα-/-) and in the macrophage/neutrophil-specific IL-4Rα-deficient mouse strain (LysMcreIL-4Rα-/lox or cre/LoxP). While 100% of T. crassiceps-infected IL-4Rα+/+ (WT) mice harbored large parasite loads, more than 50% of th eIL-4Rα-/- mice resolved the infection. Approximately 88% of the LysMcreIL-4Rα-/lox mice displayed a sterilizing immunity to the infection. The remaining few infected cre/LoxP mice displayed the lowest number of larvae in their peritoneal cavity. The inability of the WT mice to control the infection was associated with antigen-specific Th2-type responses with higher levels of IgG1, IL-4, IL-13, and total IgE, reduced NO production, and increased arginase activity. In contrast, IL-4Rα-/- semi-resistant mice showed a Th1/Th2 combined response. Furthermore, macrophages from the WT mice displayed higher transcripts for Arginase-1 and RELM-α, as well as increased expression of PD-L2 with robust suppressive activity over anti-CD3/CD28 stimulated T cells; all of these features are associated with the AAM or M2 macrophage phenotype. In contrast, both the IL-4Rα-/- and LysMcreIL-4Rα-/lox mice did not fully develop AAM or display suppressive activity over CD3/CD28 stimulated T cells, reducing PDL2 expression. Additionally, T-CD8+ but no T-CD4+ cells showed a suppressive phenotype with increased Tim-3 and PD1 expression in WT and IL-4Rα-/-, which were absent in T. crassiceps-infected LysMcreIL-4Rα-/lox mice. These findings demonstrate a critical role for the IL-4 signaling pathway in sustaining AAM and its suppressive activity during cysticercosis, suggesting a pivotal role for AAM in favoring susceptibility to T. crassiceps infection. Thus, the absence of these suppressor cells is one of the leading mechanisms to control experimental cysticercosis successfully.
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  • 文章类型: Journal Article
    已知一些寄生虫会影响脑蛋白或引起神经系统功能的变化。在这项研究中,我们的目的是证明二维凝胶技术在检测蛋白质表达差异和提供寄生虫感染期间大脑蛋白质组变化的详细信息方面是有价值的.随后,我们试图了解寄生虫感染如何影响大脑中的蛋白质组成,以及这可能与大脑功能的变化有关。通过分析感染后2、4和8周的从头表达的蛋白质,与对照小鼠的大脑相比,我们观察到2周时表达的蛋白质主要与神经保护或小鼠大脑对感染的初始反应有关。在8周的时候,寄生虫感染可以在大脑中引起氧化应激,潜在激活与细胞损伤反应相关的信号通路。在8周表达的蛋白质表现出一种模式,表明,由于宿主无法平衡生物体的神经-免疫-内分泌网络,大脑开始经历凋亡过程,因此经历脑损伤。
    Some parasites are known to influence brain proteins or induce changes in the functioning of the nervous system. In this study, our objective is to demonstrate how the two-dimensional gel technique is valuable for detecting differences in protein expression and providing detailed information on changes in the brain proteome during a parasitic infection. Subsequently, we seek to understand how the parasitic infection affects the protein composition in the brain and how this may be related to changes in brain function. By analyzing de novo-expressed proteins at 2, 4, and 8 weeks post-infection compared to the brains of the control mice, we observed that proteins expressed at 2 weeks are primarily associated with neuroprotection or the initial response of the mouse brain to the infection. At 8 weeks, parasitic infection can induce oxidative stress in the brain, potentially activating signaling pathways related to the response to cellular damage. Proteins expressed at 8 weeks exhibit a pattern indicating that, as the host fails to balance the Neuro-Immuno-Endocrine network of the organism, the brain begins to undergo an apoptotic process and consequently experiences brain damage.
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  • 文章类型: Journal Article
    最近,在吉尔吉斯斯坦,人类囊型包虫病(CE)和泡型包虫病(AE)流行。这项研究调查了2个地区的细粒棘球蚴和多房棘球蚴卵的存在;通过狗粪便中的聚合酶链反应确认了物种身份,并调查了2017-2018年寄生虫卵的环境污染水平。在Alay地区,调查了5个每年报告的AE发病率较高的村庄,即每100000个村庄中162例,而Kochkor地区的5个村庄的发病率则低得多,即每100000个村庄中21例。然而,含有S.granulosuss.l.卵的狗粪便比例在Alay和Kochkor分别为〜4.2和〜3.5%。对于多房性大肠杆菌,相应的比例为2.8%和3.2%。棘球蚴属的环境污染。使用McMaster技术估算鸡蛋的粪便卵数,犬类粪便的重量和密度。在Alay和Kochkor,多房性大肠杆菌卵的环境污染水平相似,分别为每平方米4.4和5.0个卵。E.granulosuss.l.的相应值是8.3和7.5蛋/m2。人类AE或CE的村庄或地区水平发生率与含有棘球蚴卵的狗粪便的比例之间没有关联。或环境污染的程度。秋季出现了对大黄鱼卵的污染增加,农民带着狗从夏季山区牧场返回后。
    Recently, there have been epidemics of human cystic echinococcosis (CE) and alveolar echinococcosis (AE) in Kyrgyzstan. This study investigated 2 districts for the presence of Echinococcus granulosus s.l. and Echinococcus multilocularis eggs; species identity was confirmed by polymerase chain reaction in dog feces and the level of environmental contamination with parasite eggs in 2017–2018 was also investigated. In the Alay district 5 villages with a high reported annual incidence of AE of 162 cases per 100 000 and 5 villages in the Kochkor district which had a much lower incidence of 21 cases per 100 000 were investigated. However, the proportion of dog feces containing E. granulosus s.l. eggs was ~4.2 and ~3.5% in Alay and Kochkor respectively. For E. multilocularis, the corresponding proportions were 2.8 and 3.2%. Environmental contamination of Echinococcus spp. eggs was estimated using the McMaster technique for fecal egg counts, weight and density of canine feces. The level of environmental contamination with E. multilocularis eggs was similar at 4.4 and 5.0 eggs per m2 in Alay and Kochkor respectively. The corresponding values for E. granulosus s.l. were 8.3 and 7.5 eggs per m2. There was no association between village or district level incidence of human AE or CE and the proportion of dog feces containing eggs of Echinococcus spp. or the level of environmental contamination. Increased contamination of taeniid eggs occured in the autumn, after the return of farmers with dogs from summer mountain pastures.
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  • 文章类型: Journal Article
    脑囊虫病是一种异质性疾病,患者的性别似乎在这种异质性中起作用。在腹膜内股带虫囊虫病的小鼠模型中,已经对囊虫病中的宿主性二态性进行了大量探索。在这项研究中,我们研究了由T.crusiceps引起的大鼠实质性神经囊虫病模型中炎症反应的性二态性。在Wistar大鼠的蛛网膜下腔中接种了囊尾蚴T。(25只雌性,22名男性)。90天后,对大鼠进行了组织学安乐死,免疫组织化学,和细胞因子研究。10只动物也接受了7-T磁共振成像(MRI)。雌性大鼠在蛛网膜-脑界面呈现较高浓度的免疫细胞,脑室周围区域的反应性星形胶质增生,原位促炎细胞因子(白细胞介素[IL]-6)和抗炎细胞因子(IL-10),MRI上的脑积水比男性更严重。在观察期间未观察到颅内高压信号。总的来说,这些结果提示伴随T.crusiceps脑实质外神经囊虫病的颅内炎症反应中的性二态性。
    Neurocysticercosis is a heterogeneous disease, and the patient\'s sex seems to play a role in this heterogeneity. Hosts\' sexual dimorphism in cysticercosis has been largely explored in the murine model of intraperitoneal Taenia crassiceps cysticercosis. In this study, we investigated the sexual dimorphism of inflammatory responses in a rat model of extraparenchymal neurocysticercosis caused by T. crassiceps. T. crassiceps cysticerci were inoculated in the subarachnoid space of Wistar rats (25 females, 22 males). Ninety days later, the rats were euthanized for histologic, immunohistochemistry, and cytokines studies. Ten animals also underwent a 7-T magnetic resonance imaging (MRI). Female rats presented a higher concentration of immune cells in the arachnoid-brain interface, reactive astrogliosis in the periventricular region, in situ pro-inflammatory cytokine (interleukin [IL]-6) and anti-inflammatory cytokine (IL-10), and more intense hydrocephalus on MRI than males. Intracranial hypertension signals were not observed during the observational period. Overall, these results suggest sexual dimorphism in the intracranial inflammatory response that accompanied T. crassiceps extraparenchymal neurocysticercosis.
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  • 文章类型: Journal Article
    在易感的BALB/c小鼠中,牛带虫ORF菌株的囊虫病模型在4周后显示Th2反应,允许寄生虫生长,而抗性C57BL/6小鼠产生持续的Th1反应,限制寄生生长。然而,关于囊尾蚴对耐药小鼠免疫环境的反应知之甚少。这里,我们表明Th1响应,在耐药C57BL/6小鼠感染期间,持续长达8周,并保持低寄生虫血症。在此Th1环境中寄生虫的蛋白质组学分析显示平均有128种表达的蛋白质;我们选择了15种差异表达在70%至100%之间的蛋白质。共鉴定出11种蛋白,形成4周时表达增加,8周时表达减少的群体,另一组蛋白质在2周时高表达,在8周时降低。这些鉴定的蛋白质参与组织修复,免疫调节和寄生虫的建立。这表明在Th1环境下具有抗性的小鼠中的T.crassiceps囊虫表达控制损伤并有助于在宿主中建立寄生虫的蛋白质。这些蛋白质可能是药物或疫苗开发的靶标。
    A cysticercosis model of Taenia crassiceps ORF strain in susceptible BALB/c mice revealed a Th2 response after 4 weeks, allowing for the growth of the parasite, whereas resistant C57BL/6 mice developed a sustained Th1 response, limiting parasitic growth. However, little is known about how cysticerci respond to an immunological environment in resistant mice. Here, we show that the Th1 response, during infection in resistant C57BL/6 mice, lasted up to 8 weeks and kept parasitemia low. Proteomics analysis of parasites during this Th1 environment showed an average of 128 expressed proteins; we chose 15 proteins whose differential expression varied between 70 and 100%. A total of 11 proteins were identified that formed a group whose expression increased at 4 weeks and decreased at 8 weeks, and another group with proteins whose expression was high at 2 weeks and decreased at 8 weeks. These identified proteins participate in tissue repair, immunoregulation and parasite establishment. This suggests that T. crassiceps cysticerci in mice resistant under the Th1 environment express proteins that control damage and help to establish a parasite in the host. These proteins could be targets for drugs or vaccine development.
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  • 文章类型: Journal Article
    调节宿主免疫应答的能力已经允许一些寄生虫在免疫活性生物体的组织中建立自己。虽然最近报道了一些寄生虫排泄/分泌产物(ESP)诱导调节性T细胞(Tregs)的分化,他们的身份是未知的。这项工作的目的是在体内鉴定和表征与Treg诱导相关的足带虫囊虫的ESPs。从囊尾蚴的培养物中获得ESPs,并在小鼠中接种。通过流式细胞术测量Treg水平。通过电泳分析ESP中的蛋白质;然后,ESP分为差异或保守。对差异包含的蛋白质进行MS测序并进行功能表征。10个ESP中只有4个诱导了Tregs。具有催化活性和参与免疫过程的蛋白质占主导地位,支持这些分子可以在Tregs的诱导中发挥重要作用的观点。
    The ability to modulate the host immune response has allowed some parasites to establish themselves in the tissues of an immunocompetent organism. While some parasite excretion/secretion products (ESPs) were recently reported to induce differentiation of regulatory T cells (Tregs), their identity is not known. This work is aimed to identify and characterize ESPs of Taenia crassiceps cysticerci linked with Treg induction in vivo. ESPs were obtained from cultures of T. crassiceps cysticerci and inoculated in mice, measuring Treg levels by flow cytometry. Proteins in ESPs were analyzed by electrophoresis; then, ESPs were classified as either differential or conserved. Differentially included proteins were MS-sequenced and functionally characterized. Only 4 of 10 ESPs induced Tregs. Proteins with catalytic activity and those involved in immunological processes predominated, supporting the idea that these molecules could play an important role in the induction of Tregs.
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