Immune Responses - Project C4
Determinants of semi-immunity and disease tolerance in malaria
Host labs: Florian Kurth (HUB, Charité)
Partner lab: Ian Cockburn (ANU) & Leif Sander (HUB, Charité) & CERMEL
The outcome of malaria in individual patients critically depends on their history of previous infections. Patients who have repeatedly been exposed to Plasmodium tolerate the presence of blood-stage parasites far better than those with first-time infections, e.g. with respect to organ damage. Populations of highly malaria-endemic areas even develop a state of complete absence of symptoms, despite ongoing parasitaemia. Hence, tolerance is a major determinant of what is frequently referred to as “semi-immunity”. Acquired tolerance can also be disadvantageous, particularly with respect to vaccination. For instance, whole sporozoite vaccines (PfSPZ) elicit weaker immune responses and consequently less protection in vaccinees in endemic regions than in malaria-naïve individuals.
Based on a bedside-to-bench approach, we will dissect host factors of disease tolerance in malaria-patients with different levels of acquired semi-immunity. Using samples from a) patients with first time malaria, b) patients with history of residence in malaria endemic regions who now live outside endemic regions c) patients with symptomatic and d) asymptomatic parasitaemia in an endemic region, we will perform in-depth multiparametric phenotyping to unravel critical host determinants for protection.
Methods employed include antigen specific T-cell enrichment, CyTOF and ex vivo phagocytosis assays. Analyses will be performed in close collaboration with the group of Leif Sander and a firm network within Charité. Identified pathways will be transferred to an established P. berghei mouse model in the laboratory of Ian Cockburn at ANU Canberra.
Patient-groups a) and b) will be recruited at Charité Berlin, groups c) and d) at Centre de Recherches Médicales Lambaréné (CERMEL), Gabon. The project therefore includes a 6-8 months research stay in Gabon, in addition to the times in Berlin (16 months) and Canberra (12 months).
We are looking for a motivated, flexible candidate, ideally with interest and previous experience in immunology. The position would also potentially be suitable for an MD with interest in translational research.
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