Impact of human filarial infections on the metabolic and immunological profile

非洲国家面临着现有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非洲T2D增加的原因之一，但消除寄生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反应，减轻自身免疫性疾病。最近的人体和实验动物研究表明，蠕虫通过抑制肥胖引起的炎症对T2D具有保护作用，这是T2D发病的一个重要病因。我们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提供了有益的影响，而不会引起体重减轻。该项目的主要目的是纵向评估感染曼索氏丝状线虫或盘尾丝状线虫对肥胖患者代谢和免疫学特征的影响，并将这些影响与肥胖地方性但非蠕虫感染的受试者和三组的瘦对照进行比较。我们的分析将主要包括胰岛素抵抗和脂质代谢指标，并将这些变化与肥胖、丝虫病感染状态和免疫特征变化的多变量分析相关联。我们假设感染丝虫病的肥胖患者与未感染的肥胖地方性对照相比，胰岛素敏感性得到改善，全身性炎症减少。为了提供丝虫病介导的保护作用的直接证据，在项目的第二部分，我们旨在进行一项干预研究，分析抗丝虫病治疗后代谢和免疫谱变化的动力学，以肥胖和胰岛素抵抗的进展为主要终点。该研究将在喀麦隆西南省进行，该省是波斯分枝杆菌和肠卷弧菌感染的流行地区，主要研究人员是喀麦隆布埃亚大学的Wanji教授和德国波恩大学医院的h<e:1> bner博士。波恩大学医院Hoerauf教授将作为共同申请人。拟议的项目将受益于h<s:1> bner博士在1型和2型糖尿病实验动物模型中研究丝虫病免疫调节的经验，以及Hoerauf教授和Wanji教授的联合专业知识，对人类丝虫病患者进行研究并分析其免疫反应。在拟议的项目中，我们将帮助建立一名喀麦隆青年科学家的实验室，培养两名喀麦隆博士生，并促进两名喀麦隆硕士。此外，德国合作伙伴每年将在喀麦隆举办与项目相关主题的讲习班，喀麦隆的博士生将参加在波恩提供的实践课程。

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.