Impact of human filarial infections on the metabolic and immunological profile

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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.