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Modularity in host-parasite mixed networks: interaction configuration shifts based on human perturbation and parasitism form 宿主-寄生虫混合网络中的模块化:基于人类扰动和寄生形式的交互配置变化
IF 4 2区 医学 Q1 Immunology and Microbiology Pub Date : 2023-09-01 DOI: 10.1016/j.ijpara.2023.04.004
Ana Paula Lula Costa , Jordi Bascompte , Andre Andrian Padial

Parasitism is an association based on host individual traits and environmental factors. The complexity of this type of interaction is often lost when studying species-by-species interaction networks. Here we analyze changes in modularity - a metric describing groups of nodes interacting much more frequently among themselves than they do with nodes of other modules, considering the host individual variation and the different forms of parasitism: ecto- and endo-parasitism. For this, we studied mixed networks: bipartite networks comprising host individuals and parasite species as two sets of nodes interacting with each other. We used a fish-parasite mixed network from a highly perturbed coastal river to understand how an anthropogenic perturbation gradient influences the modular structure of host-parasite networks. In addition, we tested how host individual traits drove module configuration within host-parasite mixed networks. Our results showed that different forms of parasitism respond differently to the environment: modularity in fish-ectoparasite networks increased with human perturbation, but modularity was not related to human perturbation in fish-endoparasite networks. In addition, mixed network modules were intrinsically related to individual variation, with host intensity of infection being the most important trait, regardless of the parasite’s life form. The effect of total abundance over network structure indicates signs of changes in community equilibrium, with an increase in species with opportunistic behaviors. Module composition was also related to host fitness and body size, which were most predictive in more preserved and diverse river sections. Overall, our results indicate that host-parasite networks are sensitive to ecological gradients marked by human perturbation and that host individual fitness helps to determine network structure.

寄生性是一种基于寄主个体特征和环境因素的关联。当研究物种间的相互作用网络时,这种类型的相互作用的复杂性往往会消失。在这里,我们分析了模块性的变化——考虑到宿主个体的变化和不同形式的寄生:外寄生和内寄生,模块性是一种描述节点组之间相互作用比与其他模块的节点更频繁的指标。为此,我们研究了混合网络:由宿主个体和寄生虫物种组成的二分网络,作为两组相互作用的节点。我们使用了一个来自高度扰动的沿海河流的鱼类-寄生虫混合网络来了解人为扰动梯度如何影响宿主-寄生虫网络的模块结构。此外,我们还测试了宿主个体特征如何驱动宿主-寄生虫混合网络中的模块配置。我们的研究结果表明,不同形式的寄生对环境的反应不同:鱼类外寄生虫网络的模块性随着人类的扰动而增加,但鱼类内寄生虫网络中的模块性与人类的扰动无关。此外,混合网络模块与个体变异有着内在的联系,无论寄生虫的生活形式如何,宿主的感染强度都是最重要的特征。总丰度对网络结构的影响表明群落平衡发生了变化,具有机会主义行为的物种也在增加。模块组成也与宿主的适应度和体型有关,这在保存更完好和多样化的河段最具预测性。总体而言,我们的结果表明,宿主-寄生虫网络对以人为干扰为标志的生态梯度敏感,宿主个体适应度有助于确定网络结构。
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引用次数: 0
Genome structure and population genomics of the canine heartworm Dirofilaria immitis 犬心丝虫的基因组结构和种群基因组学
IF 4 2区 医学 Q1 Immunology and Microbiology Pub Date : 2023-08-29 DOI: 10.1016/j.ijpara.2023.07.006
Javier Gandasegui , Rosemonde I. Power , Emily Curry , Daisy Ching-Wai Lau , Connor M. O'Neill , Adrian Wolstenholme , Roger Prichard , Jan Šlapeta , Stephen R. Doyle

The heartworm, Dirofilaria immitis, is a filarial parasitic nematode responsible for significant morbidity and mortality in wild and domesticated canids. Resistance to macrocyclic lactone drug prevention represents a significant threat to parasite control and has prompted investigations to understand the genetic determinants of resistance. This study aimed to improve the genomic resources of D. immitis to enable a more precise understanding of how genetic variation is distributed within and between parasite populations worldwide, which will inform the likelihood and rate by which parasites, and in turn, resistant alleles, might spread. We have guided the scaffolding of a recently published genome assembly for D. immitis (ICBAS_JMDir_1.0) using the chromosomal-scale reference genomes of Brugia malayi and Onchocerca volvulus, resulting in an 89.5 Mb assembly composed of four autosomal- and one sex-linked chromosomal-scale scaffolds representing 99.7% of the genome. Publicly available and new whole-genome sequencing data from 32 D. immitis samples from Australia, Italy and the USA were assessed using principal component analysis, nucleotide diversity (Pi) and absolute genetic divergence (Dxy) to characterise the global genetic structure and measure within- and between-population diversity. These population genetic analyses revealed broad-scale genetic structure among globally diverse samples and differences in genetic diversity between populations; however, fine-scale subpopulation analysis was limited and biased by differences between sample types. Finally, we mapped single nucleotide polymorphisms previously associated with macrocyclic lactone resistance in the new genome assembly, revealing the physical linkage of high-priority variants on chromosome 3, and determined their frequency in the studied populations. This new chromosomal assembly for D. immitis now allows for a more precise investigation of selection on genome-wide genetic variation and will enhance our understanding of parasite transmission and the spread of genetic variants responsible for resistance to treatment.

心丝虫(Dirofilaria immitis)是一种丝虫寄生线虫,对野生和驯养犬科动物的发病率和死亡率都有重大影响。对大环内酯类药物的抗药性是对寄生虫控制的一个重大威胁,促使人们对抗药性的遗传决定因素进行研究。这项研究旨在改善白喉螺虫的基因组资源,以便更准确地了解遗传变异在全球寄生虫种群内部和种群之间的分布情况,从而了解寄生虫以及抗药性等位基因传播的可能性和速度。我们利用马来布鲁氏菌(Brugia malayi)和盘尾丝虫病(Onchocerca volvulus)的染色体尺度参考基因组,指导最近发表的浮肿线虫病基因组组装(ICBAS_JMDir_1.0)的支架构建工作,最终完成了 89.5 Mb 的组装,由代表 99.7% 基因组的四个常染色体尺度支架和一个性连锁染色体尺度支架组成。利用主成分分析、核苷酸多样性(Pi)和绝对遗传差异(Dxy)评估了来自澳大利亚、意大利和美国的 32 个水蚤样本的公开和新的全基因组测序数据,以确定全球遗传结构的特征并测量种群内和种群间的多样性。这些种群遗传分析揭示了全球不同样本之间的广泛遗传结构以及种群间遗传多样性的差异;然而,精细的亚种群分析受到样本类型差异的限制和偏差。最后,我们将以前与大环内酯抗性相关的单核苷酸多态性映射到新的基因组组装中,揭示了 3 号染色体上高优先级变异的物理联系,并确定了它们在研究种群中的频率。现在,有了这种新的无尾孢蝇染色体组,就可以更精确地调查全基因组遗传变异的选择情况,并加深我们对寄生虫传播和导致抗药性的遗传变异传播的了解。
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引用次数: 0
Bovine sarcocystosis: Sarcocystis species, diagnosis, prevalence, economic and public health considerations, and association of Sarcocystis species with eosinophilic myositis in cattle 牛肌孢子虫病:牛的肌孢子虫种类、诊断、流行率、经济和公共卫生考虑因素,以及肌孢子虫与嗜酸性肌炎的关系
IF 4 2区 医学 Q1 Immunology and Microbiology Pub Date : 2023-08-01 DOI: 10.1016/j.ijpara.2022.09.009
J.P. Dubey, B.M. Rosenthal

Infections by Sarcocystis in cattle are ubiquitous worldwide. There is considerable debate concerning the identity of Sarcocystis spp. in cattle. Proper diagnosis of Sarcocystis spp. is important to assess their economic and public health importance. Currently there are seven named species: Sarcocystis hirsuta, Sarcocystis cruzi, Sarcocystis hominis, Sarcocystis bovifelis, arcocystis heydorni, Sarcocystis bovini and Sarcocystis rommeli. Additionally, there are unnamed Sarcocystis spp. Two species, S. hominis and S. heydorni, are zoonotic. One out of seven species (S. hirsuta, contracted from cats) forms macroscopic cysts which can be visible during carcass inspection. Current molecular characterization is based on DNA extracted from sarcocysts from naturally infected cattle because DNA was not characterized from tissues of experimentally infected cattle or feces of experimentally infected definitive hosts. Sarcocystis cruzi (transmitted via canids) is recognized as the most pathogenic species and it causes abortion, low milk yield, poor body growth, and outbreaks of clinical sarcocystosis and death. Additionally, Sarcocystis infections have been linked to an inflammatory condition of striated muscles termed bovine eosinophilic myositis (BEM). Cattle affected by BEM appear clinically normal. Diagnosis of BEM at slaughter occurs when inspecting the carcass surface, or once the carcass has been divided into prime cuts or quarters. Sex and breed have no apparent influence on prevalence of BEM. The condition evidently occurs with equal frequency in steers, cows, and heifers. Virtually all striated muscles can be affected including skeletal muscles, the muscles of the eye, larynx, and the heart. In the USA, regulations require condemnation of BEM-affected parts, or (in severe cases) the entire carcass. These aesthetic considerations result in economic losses. Cattle experimentally infected with Sarcocystis did not have BEM at slaughter. Here, we review the status of Sarcocystis spp. and BEM in cattle including prevalence, lesions, epidemiology, and association of BEM with different species of Sarcocystis.

牛的肉孢子虫感染在世界范围内普遍存在。关于肉孢子虫在牛身上的特性,存在着相当大的争论。正确诊断Sarcocystis spp.对评估其经济和公共卫生重要性很重要。目前有七个命名物种:多毛肉孢子虫、克鲁兹肉孢子虫,人身肉孢子虫和牛肉孢子虫。此外,还有未命名的Sarcocystis spp.两个物种,S.homonis和S.heydorni,是人畜共患的。七分之一的物种(S.hirsuta,从猫身上感染)会形成肉眼可见的囊肿,在检查尸体时可以看到。目前的分子表征是基于从自然感染牛的肌囊肿中提取的DNA,因为DNA不是从实验感染牛的组织或实验感染的最终宿主的粪便中表征的。克鲁兹肉孢子虫(通过犬科动物传播)被认为是最具致病性的物种,它会导致流产、产奶量低、身体生长不良,并引发临床上的肌囊肿病和死亡。此外,Sarcocystis感染与一种称为牛嗜酸性肌炎(BEM)的横纹肌炎症有关。受BEM影响的牛在临床上表现正常。屠宰时BEM的诊断发生在检查胴体表面时,或者一旦胴体被划分为主要切口或四分之一。性别和品种对BEM患病率没有明显影响。显然,这种情况在公牛、奶牛和小母牛身上发生的频率相同。几乎所有的横纹肌都会受到影响,包括骨骼肌、眼睛、喉咙和心脏的肌肉。在美国,法规要求谴责受BEM影响的部分,或(在严重情况下)整个胴体。这些美学考虑导致了经济损失。实验感染肉孢子虫的牛在屠宰时没有BEM。在此,我们综述了牛中肉孢子虫属和BEM的状况,包括流行率、病变、流行病学以及BEM与不同种类的肉孢子虫的关系。
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引用次数: 4
Detection of Toxoplasma gondii-specific antibodies in pigs using an oral fluid-based commercial ELISA: Advantages and limitations 猪刚地弓形虫特异性抗体的检测:优点与局限性
IF 4 2区 医学 Q1 Immunology and Microbiology Pub Date : 2023-08-01 DOI: 10.1016/j.ijpara.2022.11.003
Johanna Kauter , Filip Damek , Gereon Schares , Radu Blaga , Franziska Schott , Peter Deplazes , Xaver Sidler , Walter Basso

Toxoplasma gondii is a major food-borne parasite and undercooked meat of infected pigs represents an important source of infection for humans. Since infections in pigs are mostly subclinical, adequate diagnostic tests for use at the farm level are pursued. Oral fluid (OF) was shown to be a promising matrix for direct and indirect detection of infections with various pathogens in pigs. The objective of this study was to assess whether T. gondii infections in pigs could be diagnosed using an indirect ELISA kit adapted for OF samples (OF-ELISA). Routine serology and OF-immunoblot (IB) were used as standards for the comparison. For this, serial OF samples from sows (n = 8) and fatteners (n = 3) experimentally inoculated with T. gondii oocysts, individual field samples from potentially exposed sows (n = 9) and pooled OF samples from potentially exposed group-housed fatteners (n = 195 pig groups, including 2,248 animals) were analysed for antibodies against T. gondii by ELISA. For individual animals, OF-ELISA exhibited a relative diagnostic specificity of 97.3% and a relative diagnostic sensitivity of 78.8%. In experimentally infected animals, positive OF-ELISA results were observed from 1.5 weeks post inoculation (pi) until the end of the experimental setup (8 to 30 weeks pi); however, values below the estimated cut-off were occasionally observed in some animals despite constant seropositivity. In potentially exposed individual animals, OF- and serum-ELISA results showed 100% agreement. In group-housed fatteners, antibodies against T. gondii could be reliably detected by OF-ELISA in groups in which at least 25% of the animals were seropositive. This OF-ELISA, based on a commercially available serum-ELISA, may represent an interesting non-invasive screening tool for detecting pig groups with a high exposure to T. gondii at the farm level. The OF-ELISA may need further adjustments to consistently detect individual infected pigs, probably due to variations in OF antibody concentration over time.

弓形虫是一种主要的食源性寄生虫,感染猪的未煮熟的肉是人类感染的重要来源。由于猪的感染大多是亚临床的,因此需要进行足够的诊断测试,以便在农场层面使用。口服液(OF)被证明是一种很有前途的直接和间接检测猪各种病原体感染的基质。本研究的目的是评估是否可以使用适用于of样本的间接ELISA试剂盒(of-ELISA)诊断猪弓形虫感染。常规血清学和OF免疫印迹(IB)作为比较的标准。为此,通过ELISA分析了来自实验性接种弓形虫卵囊的母猪(n=8)和育肥者(n=3)的系列OF样本、来自潜在暴露母猪(n=9)的个体田间样本和来自潜在暴露组饲养的育肥者的合并OF样本(n=195个猪组,包括2248只动物)的抗弓形虫抗体。对于个体动物,OF-ELISA表现出97.3%的相对诊断特异性和78.8%的相对诊断敏感性。在实验感染的动物中,从接种后1.5周(pi)到实验设置结束(8至30周pi)观察到阳性OF-ELISA结果;然而,尽管血清阳性率持续,但在一些动物中偶尔会观察到低于估计临界值的值。在潜在暴露的个体动物中,OF和血清ELISA结果显示100%一致。在饲养肥猪的群体中,OF-ELISA可以在至少25%的动物血清呈阳性的群体中可靠地检测到针对弓形虫的抗体。这种基于市售血清ELISA的OF-ELISA可能是一种有趣的非侵入性筛查工具,用于检测农场水平上高暴露于弓形虫的猪群。OF-ELISA可能需要进一步调整,以一致地检测个体感染猪,这可能是由于OF抗体浓度随时间的变化。
{"title":"Detection of Toxoplasma gondii-specific antibodies in pigs using an oral fluid-based commercial ELISA: Advantages and limitations","authors":"Johanna Kauter ,&nbsp;Filip Damek ,&nbsp;Gereon Schares ,&nbsp;Radu Blaga ,&nbsp;Franziska Schott ,&nbsp;Peter Deplazes ,&nbsp;Xaver Sidler ,&nbsp;Walter Basso","doi":"10.1016/j.ijpara.2022.11.003","DOIUrl":"10.1016/j.ijpara.2022.11.003","url":null,"abstract":"<div><p><em>Toxoplasma gondii</em> is a major food-borne parasite and undercooked meat of infected pigs represents an important source of infection for humans. Since infections in pigs are mostly subclinical, adequate diagnostic tests for use at the farm level are pursued. Oral fluid (OF) was shown to be a promising matrix for direct and indirect detection of infections with various pathogens in pigs. The objective of this study was to assess whether <em>T. gondii</em> infections in pigs could be diagnosed using an indirect ELISA kit adapted for OF samples (OF-ELISA). Routine serology and OF-immunoblot (IB) were used as standards for the comparison. For this, serial OF samples from sows (<em>n</em> = 8) and fatteners (<em>n</em> = 3) experimentally inoculated with <em>T. gondii</em> oocysts, individual field samples from potentially exposed sows (<em>n</em> = 9) and pooled OF samples from potentially exposed group-housed fatteners (<em>n</em> = 195 pig groups, including 2,248 animals) were analysed for antibodies against <em>T. gondii</em> by ELISA. For individual animals, OF-ELISA exhibited a relative diagnostic specificity of 97.3% and a relative diagnostic sensitivity of 78.8%. In experimentally infected animals, positive OF-ELISA results were observed from 1.5 weeks post inoculation (pi) until the end of the experimental setup (8 to 30 weeks pi); however, values below the estimated cut-off were occasionally observed in some animals despite constant seropositivity. In potentially exposed individual animals, OF- and serum-ELISA results showed 100% agreement. In group-housed fatteners, antibodies against <em>T. gondii</em> could be reliably detected by OF-ELISA in groups in which at least 25% of the animals were seropositive. This OF-ELISA, based on a commercially available serum-ELISA, may represent an interesting non-invasive screening tool for detecting pig groups with a high exposure to <em>T. gondii</em> at the farm level. The OF-ELISA may need further adjustments to consistently detect individual infected pigs, probably due to variations in OF antibody concentration over time.</p></div>","PeriodicalId":13725,"journal":{"name":"International journal for parasitology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10020098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Short-term culture adaptation of Toxoplasma gondii archetypal II and III field isolates affects cystogenic capabilities and modifies virulence in mice 弓形虫原型II和III现场分离株的短期培养适应影响小鼠的膀胱生成能力并改变毒力
IF 4 2区 医学 Q1 Immunology and Microbiology Pub Date : 2023-08-01 DOI: 10.1016/j.ijpara.2023.03.004
Alicia Colos-Arango , Andrea Largo-de la Torre , Rafael Calero-Bernal , Luis-Miguel Ortega-Mora , Javier Regidor-Cerrillo

Most Toxoplasma gondii research has been carried out using strains maintained in the laboratory for long periods of time. Long-term passage in mice or cell culture influences T. gondii phenotypic traits such as the capability to produce oocysts in cats and virulence in mice. In this work, we investigated the effect of cell culture adaptation in the short term for recently obtained type II (TgShSp1 (Genotype ToxoDB#3), TgShSp2 (#1), TgShSp3 (#3) and TgShSp16 (#3)) and type III (#2) isolates (TgShSp24 and TgPigSp1). With this purpose, spontaneous and alkaline stress-induced cyst formation in Vero cells during 40 passages, from passage 10 (p10) to 50 (p50), and isolate virulence at p10 versus p50 were studied using a harmonized bioassay method in Swiss/CD1 mice. T. gondii cell culture maintenance showed a drastic loss of spontaneous and induced production of mature cysts after ≈25–30 passages. The TgShSp1, TgShSp16 and TgShSp24 isolates failed to generate spontaneously formed mature cysts at p50. Limited cyst formation was associated with an increase in parasite growth and a shorter lytic cycle. In vitro maintenance also modified T. gondii virulence in mice at p50 with events of exacerbation, increasing cumulative morbidity for TgShSp2 and TgShSp3 isolates and mortality for TgShSp24 and TgPigSp1 isolates, or attenuation, with absence of mortality and severe clinical signs for TgShSp16, and better control of the infection with the lowest parasite and cyst burdens in lungs and brain for the TgShSp1 isolate. The present findings show deep changes in relevant phenotypic traits in laboratory-adapted T. gondii isolates and open new discussion about their use for inferring keys to parasite biology and virulence.

大多数弓形虫的研究都是使用实验室长期保存的菌株进行的。小鼠的长期传代或细胞培养会影响弓形虫的表型特征,如猫产生卵囊的能力和小鼠的毒力。在这项工作中,我们研究了最近获得的II型分离株(TgShSp1(基因型ToxoDB#3)、TgShSp2(#1)、Tg ShSp3(#3)和Tg Shsp16(#3))和III型(#2)分离株(GgShSp24和TgPigSp1)在短期内的细胞培养适应效应。为此,在Swiss/CD1小鼠中使用协调的生物测定方法研究了Vero细胞在40代(从第10代(p10)到第50代(p50))中自发和碱性应激诱导的囊肿形成,以及在p10与p50时的分离毒力。弓形虫细胞培养维持显示,在≈25-30代后,自发和诱导产生的成熟包囊急剧减少。TgShSp1、TgShSp16和TgShSp24分离株在p50时未能产生自发形成的成熟包囊。囊肿形成有限与寄生虫生长增加和裂解周期缩短有关。体外维持也改变了小鼠在p50时的弓形虫毒力,并发生恶化事件,增加了TgShSp2和TgShSp3分离株的累积发病率和TgShSp24和TgPigSp1分离株的死亡率,或减弱,TgShSp16没有死亡率和严重临床症状,以及用TgShSp1分离物在肺和脑中最低的寄生虫和囊肿负荷更好地控制感染。目前的研究结果显示,实验室适应的弓形虫分离株的相关表型特征发生了深刻变化,并为其用于推断寄生虫生物学和毒力的关键开启了新的讨论。
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引用次数: 2
In vitro cultivation methods for coccidian parasite research 球虫体外培养方法的研究
IF 4 2区 医学 Q1 Immunology and Microbiology Pub Date : 2023-08-01 DOI: 10.1016/j.ijpara.2022.10.002
Anna Sophia Feix, Teresa Cruz-Bustos, Bärbel Ruttkowski, Anja Joachim

The subclass Coccidia comprises a large group of protozoan parasites, including important pathogens of humans and animals such as Toxoplasma gondii, Neospora caninum, Eimeria spp., and Cystoisospora spp. Their life cycle includes a switch from asexual to sexual stages and is often restricted to a single host species. Current research on coccidian parasites focuses on cell biology and the underlying mechanisms of protein expression and trafficking in different life stages, host cell invasion and host-parasite interactions. Furthermore, novel anticoccidial drug targets are evaluated. Given the variety of research questions and the requirement to reduce and replace animal experimentation, in vitro cultivation of Coccidia needs to be further developed and refined to meet these requirements. For these purposes, established culture systems are constantly improved. In addition, new in vitro culture systems lately gained considerable importance in research on Coccidia. Well established and optimized in vitro cultures of monolayer cells can support the viability and development of parasite stages and even allow completion of the life cycle in vitro, as shown for Cystoisospora suis and Eimeria tenella. Furthermore, new three-dimensional cell culture models are used for propagation of Cryptosporidium spp. (close relatives of the coccidians), and the infection of three-dimensional organoids with T. gondii also gained popularity as the interaction between the parasite and host tissue can be studied in more detail. The latest advances in three-dimensional culture systems are organ-on-a-chip models, that to date have only been tested for T. gondii but promise to accelerate research in other coccidians. Lastly, the completion of the life cycle of C. suis and Cryptosporidium parvum was reported to continue in a host cell-free environment following the first occurrence of asexual stages. Such axenic cultures are becoming increasingly available and open new avenues for research on parasite life cycle stages and novel intervention strategies.

球虫亚纲包括一大群原生动物寄生虫,包括人类和动物的重要病原体,如弓形虫、犬新孢子虫、艾美耳球虫和囊孢子虫。它们的生命周期包括从无性阶段到性阶段的转换,通常仅限于单个宿主物种。目前对球虫寄生虫的研究主要集中在细胞生物学以及不同生命阶段蛋白质表达和运输、宿主细胞入侵和宿主-寄生虫相互作用的潜在机制上。此外,还对新型抗球虫药物靶点进行了评价。鉴于研究问题的多样性以及减少和取代动物实验的要求,球虫的体外培养需要进一步发展和完善,以满足这些要求。为了这些目的,不断完善既定的文化体系。此外,新的体外培养系统最近在球虫的研究中获得了相当重要的地位。良好建立和优化的单层细胞体外培养可以支持寄生虫阶段的生存能力和发育,甚至可以在体外完成生命周期,如猪囊尾蚴和柔嫩艾美耳球虫所示。此外,新的三维细胞培养模型被用于隐孢子虫的繁殖。(球虫的近亲),由于可以更详细地研究寄生虫和宿主组织之间的相互作用,弓形虫感染三维类器官也越来越受欢迎。三维培养系统的最新进展是芯片上的组织模型,迄今为止只对弓形虫进行了测试,但有望加快对其他球虫的研究。最后,据报道,在首次出现无性阶段后,猪链球菌和细小隐孢子虫的生命周期在无宿主细胞环境中继续完成。这种无菌培养物越来越多,为研究寄生虫生命周期阶段和新的干预策略开辟了新的途径。
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引用次数: 1
Transcriptional changes associated with apoptosis and type I IFN underlie the early interaction between Besnoitia besnoiti tachyzoites and monocyte-derived macrophages 与细胞凋亡和I型IFN相关的转录变化是贝氏速殖子和单核细胞衍生巨噬细胞早期相互作用的基础
IF 4 2区 医学 Q1 Immunology and Microbiology Pub Date : 2023-08-01 DOI: 10.1016/j.ijpara.2023.05.002
María Fernández-Álvarez, Pilar Horcajo, Alejandro Jiménez-Meléndez, Carlos Diezma-Díaz, Ignacio Ferre, Iván Pastor-Fernández, Luis Miguel Ortega-Mora, Gema Álvarez-García

Besnoitia besnoiti-infected bulls may develop severe systemic clinical signs and orchitis that may ultimately cause sterility during the acute infection. Macrophages might play a relevant role in pathogenesis of the disease and the immune response raised against B. besnoiti infection. This study aimed to dissect the early interaction between B. besnoiti tachyzoites and primary bovine monocyte-derived macrophages in vitro. First, the B. besnoiti tachyzoite lytic cycle was characterized. Next, dual transcriptomic profiling of B. besnoiti tachyzoites and macrophages was conducted at early infection (4 and 8 h p.i.) by high-throughput RNA sequencing. Macrophages inoculated with heat-killed tachyzoites (MO-hkBb) and non-infected macrophages (MO) were used as controls. Besnoitia besnoiti was able to invade and proliferate in macrophages. Upon infection, macrophage activation was demonstrated by morphological and transcriptomic changes. Infected macrophages were smaller, round and lacked filopodial structures, which might be associated with a migratory phenotype demonstrated in other apicomplexan parasites. The number of differentially expressed genes (DEGs) increased substantially during infection. In B. besnoiti-infected macrophages (MO-Bb), apoptosis and mitogen-activated protein kinase (MAPK) pathways were regulated at 4 h p.i., and apoptosis was confirmed by TUNEL assay. The Herpes simplex virus 1 infection pathway was the only significantly enriched pathway in MO-Bb at 8 h p.i. Relevant DEGs of the Herpes simplex virus 1 infection (IFNα) and the apoptosis pathways (CHOP-2) were also significantly regulated in the testicular parenchyma of naturally infected bulls. Furthermore, the parasite transcriptomic analysis revealed DEGs mainly related to host cell invasion and metabolism. These results provide a deep overview of the earliest macrophage modulation by B. besnoiti that may favour parasite survival and proliferation in a specialized phagocytic immune cell. Putative parasite effectors were also identified.

感染牛瘟的公牛可能会出现严重的全身临床症状和睾丸炎,最终可能在急性感染期间导致不育。巨噬细胞可能在该疾病的发病机制和对B.besnoiti感染的免疫反应中发挥相关作用。本研究旨在在体外解剖B.besnoiti速殖子与原代牛单核细胞衍生巨噬细胞之间的早期相互作用。首先,对贝氏疟原虫速殖子的裂解周期进行了表征。接下来,通过高通量RNA测序,在感染早期(4和8小时p.i.)对B.besnoiti速殖子和巨噬细胞进行双转录组分析。用热杀速殖子(MO hkBb)和未感染巨噬细胞(MO)接种的巨噬细胞作为对照。贝氏菌能够入侵巨噬细胞并在巨噬细胞中增殖。感染后,巨噬细胞活化表现为形态学和转录组学变化。受感染的巨噬细胞较小、圆形且缺乏丝足结构,这可能与其他顶复门寄生虫表现出的迁移表型有关。在感染期间,差异表达基因(DEG)的数量显著增加。在B.besnoiti感染的巨噬细胞(MO-Bb)中,细胞凋亡和丝裂原活化蛋白激酶(MAPK)途径在感染后4小时受到调节,TUNEL检测证实了细胞凋亡。单纯疱疹病毒1型感染途径是MO-Bb在发病8小时时唯一显著富集的途径。在自然感染公牛的睾丸实质中,单纯疱疹病毒2型感染的相关DEG(IFNα)和细胞凋亡途径(CHOP-2)也受到显著调节。此外,寄生虫转录组学分析显示,DEG主要与宿主细胞的侵袭和代谢有关。这些结果为B.besnoiti最早的巨噬细胞调节提供了深入的概述,这可能有利于寄生虫在专门的吞噬免疫细胞中的生存和增殖。假定的寄生虫效应物也被鉴定出来。
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引用次数: 1
ApicoWplexa 2022: 6th international meeting on apicomplexan parasites in farm animals ApicoWplexa 2022:第六次关于农场动物中顶复门寄生虫的国际会议
IF 4 2区 医学 Q1 Immunology and Microbiology Pub Date : 2023-08-01 DOI: 10.1016/j.ijpara.2023.05.003
Andrew Hemphill, Alexandre Leitão, Luis-Miguel Ortega-Mora, Brian M. Cooke
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引用次数: 0
The turkey ascarid, Ascaridia dissimilis, as a model genetic system 火鸡蛔虫(Ascaridia dissimilis)是一种典型的遗传系统
IF 4 2区 医学 Q1 Immunology and Microbiology Pub Date : 2023-07-01 DOI: 10.1016/j.ijpara.2022.10.005
J.B. Collins, Erik C. Andersen

Parasitic nematodes cause significant effects on humans each year, with the most prevalent being Ascaris lumbricoides. Benzimidazoles (BZ) are the most widely used anthelmintic drug in humans, and although the biology of resistance to this drug class is understood in some species, resistance is poorly characterized in ascarids. Models such as Caenorhabditis elegans were essential in developing our current understanding of BZ resistance, but more closely related model nematodes are needed to understand resistance in ascarids. Here, we propose a new ascarid model species that infects turkeys, Ascaridia dissimilis, to develop a better understanding of BZ resistance.

寄生线虫每年都会对人类造成重大影响,其中最常见的是蛔虫。苯并咪唑(BZ)是人类使用最广泛的驱虫药,尽管在某些物种中对这类药物的耐药性生物学已经了解,但在蛔虫中的耐药性特征很差。秀丽隐杆线虫等模型对于发展我们目前对BZ抗性的理解至关重要,但需要更密切相关的模型线虫来理解蛔虫的抗性。在这里,我们提出了一种新的感染火鸡的蛔虫模式物种,异化蛔虫,以更好地了解BZ抗性。
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引用次数: 0
Electrophysiological characterization of a schistosome transient receptor potential channel activated by praziquantel 吡喹酮激活血吸虫瞬时受体电位通道的电生理特性
IF 4 2区 医学 Q1 Immunology and Microbiology Pub Date : 2023-07-01 DOI: 10.1016/j.ijpara.2022.11.005
Evgeny G. Chulkov , Oleg Palygin , Nawal A. Yahya , Sang-Kyu Park , Jonathan S. Marchant

Ion channels have proved to be productive targets for anthelmintic chemotherapy. One example is the recent discovery of a parasitic flatworm ion channel targeted by praziquantel (PZQ), the main clinical therapy used for treatment of schistosomiasis. The ion channel activated by PZQ – a transient receptor potential ion channel of the melastatin subfamily, named TRPMPZQ – is a Ca2+-permeable ion channel expressed in all parasitic flatworms that are PZQ-sensitive. However, little is currently known about the electrophysiological properties of this target that mediates the deleterious action of PZQ on many trematodes and cestodes. Here, we provide a detailed biophysical characterization of the properties of Schistosoma mansoni TRPMPZQ channel (Sm.TRPMPZQ) in response to PZQ. Single channel electrophysiological analysis demonstrated that Sm.TRPMPZQ when activated by PZQ is a non-selective, large conductance, voltage-insensitive cation channel that displays distinct properties from human TRPM paralogs. Sm.TRPMPZQ is Ca2+-permeable but does not require Ca2+ for channel gating in response to PZQ. TRPMPZQ from Schistosoma japonicum (Sj.TRPMPZQ) and Schistosoma haematobium (Sh.TRPMPZQ) displayed similar characteristics. Profiling Sm.TRPMPZQ responsiveness to PZQ has established a biophysical signature for this channel that will aid future investigation of endogenous TRPMPZQ activity, as well as analyses of endogenous and exogenous regulators of this novel, druggable antiparasitic target.

离子通道已被证明是驱虫化疗的有效靶点。一个例子是最近发现了吡喹酮(PZQ)靶向的寄生扁虫离子通道,吡喹酮是治疗血吸虫病的主要临床疗法。PZQ激活的离子通道是一种在所有对PZQ敏感的寄生扁虫中表达的Ca2+渗透性离子通道,PZQ是美司他汀亚家族的一种瞬态受体电位离子通道,名为TRPMPZQ。然而,目前对该靶点的电生理特性知之甚少,该靶点介导PZQ对许多吸虫和盲肠的有害作用。在这里,我们提供了曼氏血吸虫TRPMPZQ通道(Sm.TRPPZQ)对PZQ响应特性的详细生物物理表征。单通道电生理学分析表明,当被PZQ激活时,Sm.TRPMPZQ是一种非选择性、大电导、电压不敏感的阳离子通道,显示出与人类TRPM旁系不同的特性。Sm.TRPMPZQ是Ca2+可渗透的,但不需要Ca2+用于响应PZQ的通道门控。来自日本血吸虫(Sj.TRPMPZQ)和血吸虫(Sh.TRPMPZQ)的TRPMPZQ表现出相似的特征。分析Sm.TRPMPZQ对PZQ的反应性已经为该通道建立了一个生物物理特征,这将有助于未来对内源性TRPMPZQ活性的研究,以及对这种新型药物抗寄生虫靶点的内源性和外源性调节因子的分析。
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引用次数: 3
期刊
International journal for parasitology
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