Characterization of host-parasite interactions between the oral mucosa and the protozoan Entamoeba gingivalis that drive tissue invasion, destruction and microbial dysbiosis
口腔粘膜和原生动物牙龈内阿米巴之间驱动组织侵袭、破坏和微生物失调的宿主-寄生虫相互作用的表征
基本信息
- 批准号:437460519
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:德国
- 项目类别:Research Grants
- 财政年份:
- 资助国家:德国
- 起止时间:
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
Periodontitis (PD) is a common inflammatory disease of the oral cavity, with prevalence rates of 11% in Western countries for severe forms. The course of disease leads to destruction of the connective tissue of the teeth and alveolar bone with subsequent tooth loss. PD is characterized by a microbial shift of the subgingival microbiota. The dysbiosis chronically activates the immune system in predisposed individuals leading to destruction of the periodontium. Identification of a specific pathogen that drives dysbiosis, inflammation and tissue destruction would help in the diagnosis and treatment of PD. In contrast to the generally reduced microbial diversity at the sites of oral inflammation, the prevalence of the protozoan Entamoeba ginigivalis (E. gingivalis) is significantly increased, contributing the second most abundant rRNA found in PD after human rRNA. In our preliminary works, we detected E. gingivalis in 76% of inflamed periodontal pockets and in 20% of the healthy oral cavities, and gave evidence that it triggers inflammation, drives destruction of the oral barrier and is able to invade the oral mucosa where it moves and feeds on host cells. Similar to the colonic parasite E. histolytica, to which it is related, our preliminary data indicated that the invasion strategies of this oral Entamoeba species involve mucin and matrix metalloproteinase (MMP) function. The exocytosis of these proteins is orchestrated by the vesicle associated membrane proteins VAMP8 and VAMP3, respectively. Both are published genetic risk loci of PD. To elucidate the defense and infection mechanisms in detail, we will characterize the role of VAMP8 and VAMP3 in the pathogenicity of E. gingivalis infection, define the mucin and MMP-depending tissue invasion and destruction strategies, and identify the interrelation of this protozoan parasite with oral antimicrobial peptides. Additionally, we will perform de novo sequencing of the E. gingivalis genome. We will further identify the oral bacteria that are preferentially phagocytosed by E. gingivalis. Because the pathogenic mechanisms of this parasite could be an important microbial trigger of destructive forms of PD that cannot be explained by current etiological concepts, and could also contribute to an increased risk for PD-associated systemic diseases like oral cancer and cardiovascular diseases, we anticipate our results highly relevant to dental and general medicine.
牙周炎(PD)是一种常见的口腔炎症性疾病,在西方国家严重形式的患病率为11%。疾病的过程导致牙齿的结缔组织和牙槽骨的破坏和随后的牙齿脱落。PD的特点是牙龈下微生物群的微生物转移。这种生态失调会长期激活易感个体的免疫系统,导致牙周组织的破坏。识别驱动生态失调、炎症和组织破坏的特定病原体将有助于PD的诊断和治疗。与口腔炎症部位的微生物多样性普遍减少相反,原生动物牙龈内阿米巴(E. gingivalis)的患病率显著增加,是PD中发现的仅次于人类rRNA的第二丰富的rRNA。在我们的初步工作中,我们在76%的发炎牙周袋和20%的健康口腔中检测到牙龈杆菌,并提供证据表明它会引发炎症,破坏口腔屏障,并能够侵入口腔粘膜,并在那里移动并以宿主细胞为食。与大肠溶组织疟原虫相似,我们的初步数据表明,这种口腔内阿米巴的入侵策略涉及粘蛋白和基质金属蛋白酶(MMP)功能。这些蛋白的胞外分泌分别由囊泡相关膜蛋白VAMP8和VAMP3调控。两者都是已公布的帕金森病遗传风险位点。为了更详细地阐明其防御和感染机制,我们将描述VAMP8和VAMP3在牙龈杆菌感染致病性中的作用,定义黏液蛋白和mmp依赖的组织入侵和破坏策略,并确定这种原生动物寄生虫与口服抗菌肽的相互关系。此外,我们将对牙龈链球菌基因组进行从头测序。我们将进一步鉴定被牙龈杆菌优先吞噬的口腔细菌。由于这种寄生虫的致病机制可能是目前病原学概念无法解释的破坏性PD形式的重要微生物触发因素,并且还可能导致PD相关全身性疾病(如口腔癌和心血管疾病)的风险增加,我们预计我们的结果与牙科和普通医学高度相关。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Professor Dr. Arne Schäfer其他文献
Professor Dr. Arne Schäfer的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Professor Dr. Arne Schäfer', 18)}}的其他基金
Direct dissection of genomic features determining transcription factor binding, and systematic characterization of long noncoding RNAs, which are associated with an increased risk of aggressive periodontitis
直接剖析决定转录因子结合的基因组特征,以及长非编码 RNA 的系统表征,这些特征与侵袭性牙周炎的风险增加相关
- 批准号:
396785342 - 财政年份:2017
- 资助金额:
-- - 项目类别:
Research Grants
Genome-wide Association Study for the Identification of Genetic Risk Factors of Periodontitis
识别牙周炎遗传危险因素的全基因组关联研究
- 批准号:
247442915 - 财政年份:2014
- 资助金额:
-- - 项目类别:
Research Grants
Identification of genetic risk factors of periodontitis by combined QTL mapping in mice and subsequent genome-wide association analysis, sequencing, and high-throughput genotyping of patients of aggressive periodontitis
通过小鼠 QTL 联合定位以及随后的侵袭性牙周炎患者的全基因组关联分析、测序和高通量基因分型来鉴定牙周炎的遗传危险因素
- 批准号:
262320096 - 财政年份:2014
- 资助金额:
-- - 项目类别:
Research Grants
Genomweite Assoziationsstudie zur Identifikation genetischer Risikofaktoren der Parodontitis
全基因组关联研究以确定牙周炎的遗传危险因素
- 批准号:
164394054 - 财政年份:2010
- 资助金额:
-- - 项目类别:
Research Grants
Functional characterization of the long antisense noncoding RNA CDKN2BAS (ANRIL) and elucidation of the specific role in the pathophysiology of periodontitis
长反义非编码 RNA CDKN2BAS (ANRIL) 的功能表征及其在牙周炎病理生理学中的具体作用的阐明
- 批准号:
81282277 - 财政年份:2008
- 资助金额:
-- - 项目类别:
Clinical Research Units
相似国自然基金
lncRNA-HOST2—USP15—VGLL4轴促进乳腺癌肝转移的机制研究
- 批准号:82073204
- 批准年份:2020
- 资助金额:55 万元
- 项目类别:面上项目
新鉴定PA-X“host-shutoff”功能区调控H7N9禽流感病毒毒力的机制
- 批准号:
- 批准年份:2020
- 资助金额:58 万元
- 项目类别:面上项目
能量代谢触发植入干细胞和损伤视网膜细胞Graft-to Host细胞间通讯/物质交换及命运转变的机制
- 批准号:
- 批准年份:2019
- 资助金额:298 万元
- 项目类别:重点项目
溶液加工型多层磷光器件的组装与性能优化
- 批准号:51573183
- 批准年份:2015
- 资助金额:64.0 万元
- 项目类别:面上项目
Intronic miR-944联合Host gene p63在肺鳞癌中的作用机制及其诊断价值研究
- 批准号:81572275
- 批准年份:2015
- 资助金额:65.0 万元
- 项目类别:面上项目
长链非编码RNA HOST2在卵巢癌发生与转移中作用的研究
- 批准号:81172472
- 批准年份:2011
- 资助金额:68.0 万元
- 项目类别:面上项目
基于虚拟化平台支持HOST-SWAPPING机制的内存管理模型研究
- 批准号:60970125
- 批准年份:2009
- 资助金额:32.0 万元
- 项目类别:面上项目
多盘科单殖吸虫宿主特异性及其与无尾两栖类宿主协同进化关系研究
- 批准号:30960049
- 批准年份:2009
- 资助金额:23.0 万元
- 项目类别:地区科学基金项目
Jagged2high CD11bhigh 调节性树突状细胞防治cGVHD的实验研究
- 批准号:30972790
- 批准年份:2009
- 资助金额:28.0 万元
- 项目类别:面上项目
遍历理论和加性组合及其相关课题
- 批准号:10871186
- 批准年份:2008
- 资助金额:23.0 万元
- 项目类别:面上项目
相似海外基金
NSF Postdoctoral Fellowship in Biology FY 2021: Linking Parasite Genomes, Environmental Ques, and Host Phenomes Through Characterization of Behavioral Manipulation
2021 财年 NSF 生物学博士后奖学金:通过行为操纵的表征将寄生虫基因组、环境问题和宿主现象联系起来
- 批准号:
2109435 - 财政年份:2021
- 资助金额:
-- - 项目类别:
Fellowship Award
Discovery and Characterization of Capsid-Targeting Lentiviral Restriction Factors
衣壳靶向慢病毒限制因子的发现和表征
- 批准号:
10176391 - 财政年份:2019
- 资助金额:
-- - 项目类别:
Discovery and Characterization of Capsid-Targeting Lentiviral Restriction Factors
衣壳靶向慢病毒限制因子的发现和表征
- 批准号:
10647648 - 财政年份:2019
- 资助金额:
-- - 项目类别:
Discovery and Characterization of Capsid-Targeting Lentiviral Restriction Factors
衣壳靶向慢病毒限制因子的发现和表征
- 批准号:
10396652 - 财政年份:2019
- 资助金额:
-- - 项目类别:
Functional characterization of the main integral protein components of the parasite-host cell interface of Plasmodium falciparum blood stages
恶性疟原虫血液阶段寄生虫-宿主细胞界面主要整合蛋白成分的功能表征
- 批准号:
404870441 - 财政年份:2018
- 资助金额:
-- - 项目类别:
Research Grants
MOLECULAR CHARACTERIZATION OF T. GONDII MEROZOITES TO DEVELOP A CULTURE SYSTEM
弓形虫裂殖子的分子表征以开发培养系统
- 批准号:
8616949 - 财政年份:2016
- 资助金额:
-- - 项目类别:
MOLECULAR CHARACTERIZATION OF T. GONDII MEROZOITES TO DEVELOP A CULTURE SYSTEM
弓形虫裂殖子的分子表征以开发培养系统
- 批准号:
9198852 - 财政年份:2016
- 资助金额:
-- - 项目类别:
Characterization of Iron and Heme Acquisition between the Intracellular Parasite Leishmania and its Host, the Macrophage
细胞内寄生虫利什曼原虫与其宿主巨噬细胞之间铁和血红素获取的表征
- 批准号:
290007072 - 财政年份:2015
- 资助金额:
-- - 项目类别:
Research Fellowships
Characterization of nematode secreted microRNAs in host-parasite interactions
线虫分泌的 microRNA 在宿主-寄生虫相互作用中的表征
- 批准号:
300255 - 财政年份:2013
- 资助金额:
-- - 项目类别:
Fellowship Programs
Characterization of calcium signaling proteins in Toxoplasma gondii
弓形虫钙信号蛋白的表征
- 批准号:
8352190 - 财政年份:2012
- 资助金额:
-- - 项目类别: