血吸虫体被被膜蛋白质组研究进展

血吸虫成虫最外层的体被被膜由两层双分子层组成,可能涉及血吸虫营养、免疫逃避与免疫调节、排泄、渗透压调节和信号转导等重要功能,因而血吸虫体被被膜蛋白成为当今研究的热点.随着蛋白质组学研究技术的发展和应用以及血吸虫基因组计划的实施,血吸虫体被被膜蛋白质组研究取得了重要的进展.该文就近年来血吸虫被膜蛋白研究进展作一综述.     

免疫蛋白质组学技术在血吸虫病研究中的应用

蛋白质组学技术与现代免疫学相结合形成了一门新兴交叉学科——免疫蛋白质组学(immunoproteomics).日本血吸虫和曼氏血吸虫的基因组、转录组研究积累了大量生物信息资料,使血吸虫免疫蛋白质组研究成为可能.该文对近几年来免疫蛋白组学技术在血吸虫病研究中的应用进行综述.     

结核杆菌转录组学研究进展

自1998年结核分枝杆菌H37Rv菌株的全基因组测序完成以后,结核杆菌转录组学的研究就变得异常活跃,特别是随着高通量的基因芯片技术应用于结核菌转录组学的研究,结核杆菌转录组学的进展更加迅猛.结核杆菌转录组学研究经历了由体外分离株到巨噬细胞吞噬体内结核杆菌,从结核杆菌在体外的表达到在宿主体内表达,而宿主由以小鼠为模型到以人体为模型的研究过程.由于以动物为模型的便利性,当前结核杆菌转录组学研究以基因突变小鼠为模型或药物作用后的小鼠结核感染模型为主.这些研究为抗结核药物研究和临床诊断提供必要的基础信息.本文对结核杆菌的转录组学研究作一综述.     

血吸虫体被的结构功能及其蛋白质组研究

血吸虫体表由一层合抱体细胞组成,称为体被。体被在血吸虫的营养吸收和免疫逃避等方面发挥重要作用,也被认为是诊断、疫苗和药物的潜在靶点。近年来兴起的体被蛋白质组研究,迄今已发现和鉴定了一大批体被蛋白,这将为血吸虫病的预防控制提供重要线索。     

脂类在曼氏血吸虫体内的特殊作用

曼氏血吸虫不能完整合成自身所需要的脂类,必须从宿主获得脂类。脂类不仅对血吸虫完成生活史,而且对其逃避宿主免疫攻击具有重要作用。本文描述了脂类的作用以及血吸虫获得脂类的途径。     

血吸虫与宿主相互关系的研究进展

血吸虫侵入宿主后对宿主产生损害,同时宿主会设法清除感染的血吸虫,血吸虫与宿主相互作用于对方,在长期共进化中形成了复杂的相互适应机制.近年来,血吸虫-宿主相互关系中研究较多的是免疫学关系,如宿主免疫调节、血吸虫免疫逃避等.血吸虫谷胱苷肽S转移酶等分子对宿主具有免疫保护性作用.     

血吸虫及其相关产物在宿主免疫调节中的作用

血吸虫可通过合成、分泌或者排泄多种具有免疫调节功能的分子影响宿主的免疫系统,主要表现为促进Th2免疫效应,抑制Th1/Th17免疫效应.血吸虫感染过程中,其免疫调节效应可以调控宿主固有免疫和适应性免疫,使其能够逃避宿主的免疫攻击,而在人体内长期存活.研究显示血吸虫感染对于过敏性疾病、自身免疫性疾病以及同种异体免疫反应等...     

一种可能参与寄生虫内部及宿主与寄生虫信号的曼氏血吸虫脑啡肽能系统

曼氏血吸虫逃避,或至少部分逃避中间宿主及终宿主的免疫应答。近几年,作者对血吸虫在免疫逃避中神经多肽的参与进行了研究。经放射免疫分析发现,在曼氏血吸虫毛蚴、尾蚴、童虫和成虫各期,都有与促肾上腺皮质素、促黑素细胞激素及β-内啡肽相关的分子。还发现在不同生活阶段,这些生物活性多肽被释放并影响宿主的免疫应答,表明血吸虫和宿主能通过这些它们共有的信号     

血吸虫的免疫力:靶子

过去十年,在血吸虫免疫学范畴里,大量研究工作正朝着长远的目标——生产一种有效的抗血吸虫疫苗努力。这种疫苗的研制似乎取决于对血吸虫表面生物学的进一步了解。现有的研究结果表明,血吸虫童虫的表面抗原对宿主的免疫攻击起着靶子的作用。这些靶抗原随着血吸虫的发育而瞒着宿主隐藏下来,这样就逃避了宿主的免疫。     

血吸虫免疫逃避机制的研究现状

血吸虫免疫逃避机制是血吸虫抵抗宿主而得以存活的重要因素,目前较肯定的机制主要是抗原改变和免疫调节.抗原改变主要是血吸虫抗原的变异、模拟和伪装,使宿主的免疫临视功能敏感度下降;免疫调节主要是血吸虫通过合成神经分子、蛋白酶、细胞因子及其他小分子物质,阻断宿主补体的激活,抑制宿主的免疫细胞功能,从而下调宿主的免疫功能,这两种机制均有利于血吸虫在宿主体内的存活.     

Reverse genetics and the study of the immune response to schistosomes

The sequencing of the schistosome genome and the establishment of techniques for RNAi and transient transfection in these parasites have opened the door for a reverse genetics approach to studying schistosomes. One of the most intriguing aspects of schistosome biology is the interaction of these parasites with the immune system. The immune response underlies the ability of the host to survive while infected and to eventually develop resistance to further infection. However, it is also instrumental in the development of disease due to its role orchestrating granuloma formation around tissue-trapped parasite eggs. While schistosomes have clearly evolved mechanisms for evading host immune responses, their normal development is, paradoxically, also dependent upon the presence of a normal immune system. This article will review recent advances in the development of tools for studying gene function in schistosomes, and discuss how these new tools may be exploited to investigate issues of key importance in the interaction of schistosomes with the host immune system.     

Hepatobiliary Schistosomiasis

Schistosomiasis is an ancient parasitic disease that has afflicted Egyptians since the time of the pharaohs. The disease is caused by lodged schistosome eggs in the host liver, evoking an immune response and leading in some patients to the development of hepatic granuloma and fibrosis. Here, we review the epidemiology, immunopathogenesis, and clinical profile of schistosomiasis. This information may aid in the development of more efficacious treatments and improved disease prognosis.     

Immunopathogenesis of human schistosomiasis

Schistosomiasis continues to be a significant cause of parasitic morbidity and mortality worldwide. This review considers the basic features of the pathology and clinical outcomes of hepatointestinal and genitourinary schistosomiasis, presents an overview of the numerous studies on animal models that have clarified many of the immunopathological features, and provides insight into our current understanding of the immunopathogenesis and genetic control of human schistosomiasis. In murine schistosomiasis, pathology is induced by a CD4⁺ Th2 driven granulomatous response directed against schistosome eggs lodged in the host liver. The Th2 cytokines IL-4 and IL-13 drive this response, whereas IL-10, IL13Rα2, IFN-γ and a subset of regulatory T-cells act to limit schistosome induced pathology. A variety of cell types including hepatic stellate cells, alternatively activated macrophages and regulatory T-cells have also been implicated in the pathogenesis of schistosomiasis. Current knowledge suggests the immunopathogenic mechanisms underlying human schistosomiasis are likely to be similar. The review also considers the future development of anti-pathology schistosome vaccines. As fibrosis is an important feature of many other diseases such as Crohn's disease and sarcoidosis, a comprehensive understanding of the cellular and molecular mechanisms involved in schistosomiasis may also ultimately contribute to the development an effective disease intervention strategy for other granulofibrotic diseases.     

Association of in utero sensitization to Schistosoma haematobium with enhanced cord blood IgE and increased frequencies of CD5- B cells in African newborns

This study investigated in utero priming as a consequence of maternal parasitic infections. Cord blood plasma samples of 63 African newborns were assessed by enzyme-linked immunosorbent assay for their content of total and schistosome-specific or filaria-specific IgE and IgG4. The frequencies of lymphocyte phenotypes in cord blood were also determined by using flow cytometry, and were compared with those of European newborns. We found significantly increased schistosome soluble egg antigen (SEA)-specific IgE in cord plasma of those born to mothers with schistosome infections and correlations between fetal and maternal SEA-specific and filaria antigen-specific IgE. These data are evidence for in utero priming of the fetal immune system to maternal helminth infections. Furthermore, we show significantly enhanced percentages of CD5- B cells in African newborns cord blood compared with Europeans, which is consistent with earlier maturation of the African fetal immune system.     

荧光原位杂交技术在血吸虫生物学中的应用及进展

血吸虫病是危害最为严重的寄生虫病之一。深入探索血吸虫功能基因可为该病的诊断、疫苗和药物靶点研究提供基础和依据。荧光原位杂交技术可用于血吸虫的功能基因在染色体上定位、构建基因组物理图谱和染色体识别等方面的研究。本文就荧光原位杂交技术在血吸虫研究中的应用,以及将来可行的研究方向作一简要综述。     

Schistosome glycans and innate immunity

Schistosome glycans induce characteristic innate immune responses in the infected host. The molecular aspects of these responses, the pathways and receptors as well as the schistosome glycans and glycoconjugates involved, form an area of intense research. The relevant schistosome glycan elements and the possible mechanisms through which they act on the innate immune system are discussed in this review.     

Apoptosis, a protective mechanism for pathogens and their hosts

In this review we summarize the great amount of recent information on the apoptosis in aspects of the host-parasite interaction. Although apoptosis is a form of programmed cell death which plays a pivotal role in normal tissue development a plethora of pathogens including parasitic protista and helminths are able to modulate host apoptosis pathways to their own advantage. Here in we present and discuss new research data and results describing the phenomenon as a process have been controlled by gene expression, biochemical reactions and receptor-ligand interactions at the cell membrane surface. Section 1 describes apoptosis as ongoing process in normal tissue development. Section 2 analyzes the role of apoptosis in outcome of infection and pathogenesis of several disorders evoked by viruses and bacteria. The cellular mechanisms of cell death during infection with unicellular parasites such as Leishmania sp. and Plasmodium sp. are described in Section 3. In the next paragraph the potency of parasitic protista and helmiths for modulation host apoptosis pathways to their own advantage is discussed. The involvement of apoptosis in immunoregulation of the host immune function was proposed as a one of possible mechanism in creation of the host-parasite relationship. The molecular and cellular mechanisms of parasite-induced immune response via apoptosis pathways are discussed. We conclude that novel strategies for the management of the host-parasite relationships need to be explained into the mechanisms by which parasites induced apoptosis in contribution to the activity of immune system of the host.     

Genetic epidemiology of human schistosomiasis in Brazil

Human schistosomiasis presents the classic, complex disease phenotype, with marked variation in the intensity of infection, the immune response to infection, and the development of schistosome-related pathology. Determining the role of host genetics in schistosomiasis is complicated by the numerous parasite and environmental factors involved in transmission. However, as a result of the increased availability of sequence data, novel statistical methods, and new methods of study design, the last decade has seen significant advances in identifying the role of host genetics in schistosome infection around the world. Many of these advances have taken place in Brazil. Epidemiological studies in Brazil have shown that the intensity of infection (worm burden) is a heritable phenotype (41%). Human genome scans have identified a locus responsible for controlling Schistosoma mansoni infection intensity on chromosome 5q31-q33. There is also evidence for genetic control of pathology due to S. mansoni, with linkage reported to a region containing the gene for the interferon-gamma receptor 1 subunit. Numerous association studies have also provided evidence for major histocompatibility complex control of pathology in schistosomiasis. Recent candidate gene studies suggest a role of other immune response genes in controlling helminth infection and pathology. We chronicle the many advances made in understanding the role of host genetics in S. mansoni infection that have taken place in Brazil by phenotype studied: infection intensity, immune response, and disease development. Results from Brazilian studies are compared with studies of S. mansoni and other schistosome species elsewhere in the world.     

Functional genomics approaches in parasitic helminths

As research on parasitic helminths is moving into the post-genomic era, an enormous effort is directed towards deciphering gene function and to achieve gene annotation. The sequences that are available in public databases undoubtedly hold information that can be utilized for new interventions and control but the exploitation of these resources has until recently remained difficult. Only now, with the emergence of methods to genetically manipulate and transform parasitic worms will it be possible to gain a comprehensive understanding of the molecular mechanisms involved in nutrition, metabolism, developmental switches/maturation and interaction with the host immune system. This review focuses on functional genomics approaches in parasitic helminths that are currently used, to highlight potential applications of these technologies in the areas of cell biology, systems biology and immunobiology of parasitic helminths.