Lectin-Carbohydrate Interactions in the Host-Parasite System

宿主-寄生虫系统中的凝集素-碳水化合物相互作用

• 批准号: 7641509
• 负责人: XIAO-QIANG YU
• 金额: $ 22.35万
• 依托单位: UNIVERSITY OF MISSOURI KANSAS CITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-08 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7641509
• 关键词: Affinity; Binding; Biochemical; Brugia malayi; Brugia pahangi; C-Type Lectins; Caenorhabditis elegans; Calcium; Carbohydrates; Cells; Communicable Diseases; Culicidae; Detection; Dirofilaria immitis; Evolution; Filariasis; Glycoproteins; Immune response; Immune system; Infection; Insecta; Invertebrates; Lectin; Ligand Binding; Malaria; Manduca; Manduca sexta; Masks; Mediating; Membrane Proteins; Microfilaria; Molecular; Monophenol Monooxygenase; Mycoses; Natural Immunity; Nematoda; Organism; Outcome; Parasites; Pattern; Pattern Recognition; Pattern recognition receptor; Polysaccharides; Protein C; Protein Family; Proteins; Role; Specificity; Surface; System; Variant; Vertebrates; killings; microbial; pathogen; prototype; public health relevance; receptor; receptor binding; vector

DESCRIPTION (provided by applicant): Parasites are causative agents of some insect-borne infectious diseases such as malaria and filariasis. Insects respond to infection by parasites with both cellular and humoral immune responses. However, parasites have developed strategies to evade or suppress immune responses of their vectors. Insects must first recognize pathogens before they can mount an immune response, and recognition of nonself infective agents is mediated by pattern recognition receptors (PRRs). We have some understanding of the proteins that serve as PRRs in insects to stimulate immune responses to bacterial or fungal infection. However, very little is known about how insect immune systems recognize eukaryotic parasites and how these parasites evade the host immune system. We propose that parasites have variations in the molecular character of their surface, which determine selective binding of host proteins to parasites and the fate of parasites. The C-type lectins are a family of proteins with functions as PRRs in innate immunity. We have identified a group of C-type lectins (immulectins) from the tobacco hornworm Manduca sexta, which function as PRRs to stimulate immune responses. Immulectin-2 (IML-2) directly binds to nematodes Caenorhabditis elegans and Brugia malayi, and binding of IML-2 to C. elegans stimulates melanization of the worms. However, C-type lectins from mosquitoes have not been well characterized, particularly with regard to biochemical functions. Thus, we will use two systems, M. sexta - nematodes and the mosquito Armigeres subalbatus - filarial nematodes, to study interactions of IML-2 and Armigeres C-type lectins with microfilariae, and to study the roles of IML-2 and Armigeres lectins in melanotic encapsulation of microfilariae. The two specific aims are: 1) Investigate molecular interaction of an insect prototype C-type lectin, Manduca immulectin-2, with nematodes (B. malayi, B. pahangi, D. immitis, and C. elegans) as a guide to understanding potential lectin-parasite interactions that influence the outcome of pattern recognition and innate immune responses. 2) Investigate the ligand-binding specificity and affinity of nine selected Armigeres C-type lectins for microfilariae (B. malayi, B. pahangi, and D. immitis), and study functions of these lectins in melanotic encapsulation of microfilariae in Ar. subalbatus. Identify surface proteins or surface polysaccharides of C. elegans and B. malayi that can be recognized by Manduca immulectin-2 or Armigeres C-type lectins. PUBLIC HEALTH RELEVANCE Parasites are causative agents of some insect-borne infectious diseases such as malaria and filariasis. Insects respond to infection by parasites with both cellular and humoral immune responses. However, insects must first recognize pathogens before they can mount an immune response, and recognition of nonself infective agents is mediated by pattern recognition receptors (PRRs). We have some understanding of the proteins that serve as PRRs in insects to stimulate immune responses to bacterial or fungal infection. However, very little is known about how insect immune systems recognize non-fungal eukaryotic parasites: what are the pathogen-associated molecular patterns on such organisms and what PRRs bind to them? The C-type (calcium-dependent) lectins are a family of proteins with functions as PRRs in innate immune systems of vertebrates and invertebrates. This project is to investigate how selective binding of host proteins to parasites determines the fate of parasites using two systems, the tobacco hornworm Manduca sexta - nematodes and the mosquito Armigeres subalbatus - filarial nematodes.

描述（由申请人提供）：寄生虫是某些昆虫传染病（例如疟疾和丝虫病）的病原体。昆虫对寄生虫的感染反应，并具有细胞和体液免疫反应。但是，寄生虫已经制定了逃避或抑制其媒介免疫反应的策略。昆虫必须首先识别病原体，然后才能实现免疫反应，并且对非自然感染剂的识别是由模式识别受体（PRR）介导的。我们对在昆虫中充当PRR的蛋白质有所了解，以刺激对细菌或真菌感染的免疫反应。但是，关于昆虫免疫系统如何识别真核寄生虫以及这些寄生虫如何逃避宿主免疫系统的知之甚少。我们建议寄生虫在其表面的分子特征上具有变化，这些特征决定了宿主蛋白与寄生虫和寄生虫的命运的选择性结合。 C型凝集素是一个具有先天免疫力的PRR的蛋白质家族。我们已经确定了一组来自烟草nort虫甘达·塞克斯塔（Manduca sexta）的C型凝集素（免疫素），该蛋白虫是刺激免疫反应的PRR。免疫蛋白2（IML-2）直接与线虫秀丽隐杆线虫和马来语结合，IML-2与秀丽隐杆线虫的结合刺激了蠕虫的黑素化。但是，蚊子的C型凝集素尚未得到很好的特征，尤其是在生化功能方面。因此，我们将使用两个系统，即M. sexta-nematodes和蚊子Armigeres subalbatus-filararial nematodes，研究IML-2和Armigeres C型凝集素与微生物菌的相互作用，并研究IML-2和Armigeres lectins lectins in Iml-2和Armigeres lectins in Microforilariae的作用。这两个具体目的是：1）研究昆虫原型C型凝集素，甘达免疫-2的分子相互作用，以及线虫（B. Malayi，B。Pahangi，D。immitis and C. exlemans），作为理解潜在的静脉蛋白 - 寄生虫相互作用的指南，这些相互作用会影响潜在的型型静态识别识别和固有免疫反应的结果。 2）研究了九个选定的Armigeres c型凝集素的配体结合特异性和亲和力（B. Malayi，B。Pahangi和D. immitis），以及这些凝集素在AR中微分乳房中属于素虫的封装中的研究功能。亚albatus。鉴定秀丽隐杆线虫和马来语的表面蛋白质或表面多糖可以通过甘达免疫蛋白-2或Armigeres C型凝集素识别。公共卫生相关性寄生虫是一些昆虫传染病（例如疟疾和丝虫病）的病因。昆虫对寄生虫的感染反应，并具有细胞和体液免疫反应。但是，昆虫必须先识别病原体才能实现免疫反应，并且对非自然感染剂的识别是由模式识别受体（PRR）介导的。我们对在昆虫中充当PRR的蛋白质有所了解，以刺激对细菌或真菌感染的免疫反应。但是，关于昆虫免疫系统如何识别非真实真核寄生虫的了解很少：这种生物上与病原体相关的分子模式是什么？ C型（依赖钙）凝集素是蛋白质家族，具有脊椎动物和无脊椎动物的先天免疫系统中的PRR。该项目是为了研究宿主蛋白与寄生虫的选择性结合如何使用两个系统，即烟草Hornworm manduca sexta -nematodes -nematodes和Mosquito Armigeres subalbatus -Filararial nematodes决定寄生虫的命运。