The zymogen granule membrane glycoprotein 2 (GP2) as trigger for host tropism and individuality of intestinal infections.

酶原颗粒膜糖蛋白 2 (GP2) 作为宿主向性和肠道感染个体性的触发因素。

• 批准号: 288074052
• 负责人: Professor Dr. Peter Schierack
• 金额: --
• 依托单位: Fachgebiet Multiparameterdiagnostik
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/288074052?language=en
• 关键词: zymogen; granule; membrane; glycoprotein; GP2

The zymogen granule membrane glycoprotein 2 (GP2) is expressed by the follicle associated epithelium of the intestine, affects intestinal infections via binding of the bacterial adhesin FimH, might play a role in Crohns disease and is an immunomodulator of the innate as well as acquired immunity. In our previous work using Enterobacteriaceae we showed that binding to GP2 is specific for single bacterial species or pathotypes but also specific for host animal species.Based upon our comprehensive preliminary work we would like to clarify in detail mechanisms of this phenomenon by means of the following hypothesis: bacterial intestinal infections are often host specific and individual. GP2 and its interactions with bacteria on the one hand and effects via intestinal epithelial cells to cells of the intestinal immune system on the other hand are basics for host tropism and individuality.In our preliminary work we used only one out of four described human GP2 isoforms. Since GP2 of other mammal species is unknown yet, we will define other mammal GP2 including possible isoforms. GP2 and GP2 isoforms are compared to each other. For identification of new GP2 we screen published DNA sequences for sequences homologue to GP2 or use tissues of pigs or cattle to generate cDNA. Identified GP2 types and isoforms are recombinantly expressed. We perform binding studies in a screening format using GP2 proteins and 400 well defined bacterial isolates. In parallel, we transduce cell lines to express each GP2 isoform in its host specific background. These cells are used for adhesion and invasion studies. In addition, cell lines of phagocytes are incubated with fluorescence labelled bacteria (phagocytosis assays). Finally, we perform first in vitro infection studies to show whether recombinant GP2 can inhibit bacterial infections.

酶原颗粒膜糖蛋白2（GP 2）由肠的滤泡相关上皮表达，通过结合细菌粘附素FimH影响肠感染，可能在克罗恩病中起作用，并且是先天性和获得性免疫的免疫调节剂。在我们以前的工作中使用肠杆菌科，我们表明，结合GP2是特异性的单一细菌种或致病型，但也特异性宿主动物specials.Based上我们全面的初步工作，我们想澄清在详细的机制，这种现象通过以下假设：细菌肠道感染往往是宿主特异性和个人。GP2及其与细菌的相互作用以及通过肠上皮细胞对肠免疫系统细胞的影响是宿主嗜性和个体性的基础。在我们的初步工作中，我们仅使用了四种已描述的人类GP2同种型中的一种。由于其他哺乳动物物种的GP2是未知的，我们将定义其他哺乳动物GP2，包括可能的亚型。将GP2和GP2同种型相互比较。为了鉴定新的GP2，我们筛选已发表的DNA序列中与GP2同源的序列，或使用猪或牛的组织产生cDNA。重组表达鉴定的GP2类型和同种型。我们使用GP 2蛋白和400种明确定义的细菌分离株以筛选形式进行结合研究。同时，我们对细胞系进行测序，以在其宿主特异性背景中表达每种GP2同种型。这些细胞用于粘附和侵袭研究。此外，将吞噬细胞的细胞系与荧光标记的细菌一起孵育（吞噬测定）。最后，我们进行了第一次体外感染研究，以显示重组GP2是否可以抑制细菌感染。