Impact of human filarial infections on the metabolic and immunological profile

人类丝虫感染对代谢和免疫学特征的影响

• 批准号: 380545624
• 负责人: Professor Dr. Marc Hübner
• 金额: --
• 依托单位: Department of Microbiology and Parasitology
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/380545624?language=en
• 关键词: Impact; human; filarial; infections; metabolic

African nations are confronted with existing infectious diseases and upcoming non-communicable diseases such as type 2 diabetes (T2D). While rapid cultural and social changes are thought to contribute to this increase of T2D in Africa, elimination of helminth infections may be a contributing factor. Helminths modulate the host’s immune system thereby impacting immune responses to bystander antigens and mitigating autoimmune diseases. Recent human and experimental animal studies suggest that helminths confer a protective role on T2D by suppressing obesity-induced inflammation, which is an important etiological factor for the pathogenesis of T2D. Studies on diet-induced obese mice from our lab show that filarial immunomodulation provides such a beneficial impact on diet-induced glucose intolerance without inducing weight loss.The primary aim of this project is to longitudinally assess the impact of infections with the filarial nematodes Mansonella perstans or Onchocerca volvulus on the metabolic and immunological profile of obese patients and to compare those with obese endemic but non-helminth infected subjects and lean counterparts of the three groups. Our analysis will primarily encompass indicators for insulin resistance and lipid metabolism and correlate those changes in a multivariate analysis to obesity, filarial infection status and changes in the immunological profile. We hypothesize that filariae-infected obese patients will have an improved insulin sensitivity and a reduced systemic inflammation compared to obese non-infected endemic controls. In order to provide direct evidence of the filariae-mediated protective effect, in the second part of the project, we aim to perform an intervention study analyzing the kinetics of changes in the metabolic and immunological profiles after anti-filarial treatment with progression of obesity and insulin resistance as primary endpoints. The study will be performed in the Southwestern Province of Cameroon, which is an endemic area for M. perstans and O. volvulus infections, in collaboration of the principal investigators Prof. Wanji, University of Buea, Cameroon, and Dr. Hübner, University Hospital of Bonn, Germany. Prof. Hoerauf, University Hospital of Bonn, will act as co-applicant. The proposed project will benefit from Dr. Hübner’s experience in studying filarial immunomodulation in experimental animal models of type 1 and type 2 diabetes with the combined expertise of Prof. Hoerauf and Prof. Wanji to conduct studies with human filariasis patients and the analyses of their immune responses. Within the proposed project we will help to establish the lab of one young scientist from Cameroon, train two Cameroonian PhD students and facilitate two MSc in Cameroon. Furthermore, workshops on project related topics will be provided by the German partner on a yearly basis in Cameroon and Cameroonian PhD students will participate in practical courses provided in Bonn.

非洲国家面临着现有的传染病和即将到来的非传染性疾病，如2型糖尿病（T2D）。虽然快速的文化和社会变化被认为是导致非洲T2D增加的原因，但消除蠕虫感染可能是一个促成因素。蠕虫调节宿主的免疫系统，从而影响对旁观者抗原的免疫应答并减轻自身免疫性疾病。最近的人类和实验动物研究表明，蠕虫通过抑制肥胖诱导的炎症对T2D具有保护作用，肥胖诱导的炎症是T2D发病机制的重要病因因素。本实验室对饮食诱导的肥胖小鼠的研究表明，丝虫免疫调节对饮食诱导的葡萄糖耐受不良具有有益的影响，而不诱导体重减轻。本项目的主要目的是纵向评估丝虫线虫Mansonella perstans或盘尾丝虫旋绕感染对肥胖患者代谢和免疫特征的影响，并比较肥胖地方性但非地方性肥胖患者的代谢和免疫特征。蠕虫感染的受试者和三组的瘦对照。我们的分析将主要包括胰岛素抵抗和脂质代谢的指标，并在多变量分析中将这些变化与肥胖、丝虫感染状况和免疫学特征的变化相关联。我们假设丝虫感染的肥胖患者将有一个改善的胰岛素敏感性和减少全身炎症相比，肥胖的非感染的地方病对照。为了提供丝虫介导的保护作用的直接证据，在该项目的第二部分，我们的目标是进行干预研究，分析抗丝虫治疗后代谢和免疫特征变化的动力学，以肥胖和胰岛素抵抗的进展为主要终点。这项研究将在喀麦隆西南部省进行，该省是M. perstans和O.扭转感染，主要研究者Wanji教授，喀麦隆布埃亚大学，和Hübner博士，波恩大学医院，德国合作。波恩大学医院的Hoerauf教授将作为共同申请人。拟议的项目将受益于Hübner博士在1型和2型糖尿病实验动物模型中研究丝虫免疫调节的经验，以及Hoerauf教授和Wanji教授在人类丝虫病患者中进行研究及其免疫反应分析的综合专业知识。在拟议的项目中，我们将帮助建立一个来自喀麦隆的年轻科学家的实验室，培训两名喀麦隆博士生，并促进喀麦隆的两个硕士学位。此外，德国合作伙伴将每年在喀麦隆举办与项目有关的专题讲习班，喀麦隆的博士生将参加在波恩举办的实践课程。