Analysis of Host-Parasite Cross-Talk based on the Bovine Model for Human Onchocerciasis, Onchocerca ochengi
Final Report Abstract
Helminths parasitize for long periods of time in their immuncompetent hosts, provoking only restricted pathology in their tissue habitats although the pathogens can amount to large sizes. Because of their largeness, helminths cannot sequester in niches like many bacteria, fungi and protozoa. By co-evolution, these “king-sized” pathogens have developed other strategies to secure survival. Here molecules are of importance that are secreted into the host tissue or are associated with the surface of the parasite. They represent the first molecules exposed to and affecting the host immune apparatus and are thus likely to be involved in the establishment and maintenance of the parasite within the host and in the avoidance, modulation and skewing of the host immune response. Immune modulation is suggested to be beneficial to both, the human host and the parasite, as it protects the worm from being eradicated, and at the same time protects the host from excessive inflammatory responses that may lead to tissue damage. In our multidisciplinary project based on 30 years of field research in Ngaoundere and a welldeveloped network between German and Cameroonian scientists, we integrated molecular and structural biology with immunology and epidemiological and entomological fieldwork, to understand how helminths suppress and modulate the sophisticated host immune system and communicate. We analysed excretory/secretory products (ESPs) from Onchocerca parasites that were implicated to play a role in parasite-host interaction. By applying a combination of masspectrometry techniques we identified low molecular peptides (32 peptides derived from Onchocerca proteins, 9 not yet assigned peptides). Furthermore, we identified potential vaccine candidates , i.e. ES proteins that were targeted by humoral and cellular immune effectors, while other ES proteins suppressed T cell activation. By using the model nematode Caenorhabditis elegans, we were able to identify the physiological function of several proteins that were identified by mass spectrometric analysis of collected ESPs from Onchocerca ochengi, a bovine filaria highly endemic in cattle in Cameroon and the closest relative to O. volvulus, the agent of human onchocerciasis. Our results from the bovine model can be directly transferred to the human parasite, which is also highly prevalent and intrinsingly intermixed with bovine onchocercosis. In our project we can also point to notable achievements in capacity and infrastructure building in Ngaoundere, Cameroon. Training of students and young scientist in the endemic area of Ngaoundere was conducted and the skills of the personnel and the state of laboratory methods at the University of Ngaoundere was highly improved.
Publications
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(2011) Life cycle stage-resolved proteomic analysis of the excretome/secretome from Strongyloides ratti-- identification of stage-specific proteases. Mol Cell Proteomics. 10(12):M111.010157
Soblik H, Younis AE, Mitreva M, Renard BY, Kirchner M, Geisinger F, Steen H, Brattig NW
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(2011) Stage-specific excretory-secretory small heat shock proteins from the parasitic nematode Strongyloides ratti--putative links to host's intestinal mucosal defense system. FEBS J. 278(18):3319-36
Younis AE, Geisinger F, Ajonina-Ekoti I, Soblik H, Steen H, Mitreva M, Erttmann KD, Perbandt M, Liebau E, Brattig NW
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(2012) Functional characterization and immune recognition of the extracellular superoxide dismutase from the human pathogenic parasite Onchocerca volvulus (OvEC-SOD). Acta Trop. 124(1):15-26
Ajonina-Ekoti I, Ndjonka D, Tanyi MK, Wilbertz M, Younis AE, Boursou D, Kurosinski MA, Eberle R, Lüersen K, Perbandt M, Breloer M, Brattig NW, Liebau E
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(2012) Single worm genotyping demonstrates that Onchocerca ochengi females simultaneously produce progeny sired by different males. Parasitol Res. 111(5):2217-21
Hildebrandt JC, Eisenbarth A, Renz A, Streit A
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(2012) Vaccination with Strongyloides ratti heat shock protein 60 increases susceptibility to challenge infection by induction of Th1 response. Vaccine. 30:862-71
Nouir NB, Eschbach ML, Piédavent M, Osterloh A, Kingsley MT, Erttmann K, Brattig N, Liebau E, Fleischer B, Breloer M
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(2013) Filarial parasites possess an antizyme but lack a functional ornithine decarboxylase. Acta Trop. 126(3):167-76
Kurosinski MA, Lüersen K, Ndjonka D, Younis AE, Brattig NW, Liebau E
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(2013) Molecular evidence of 'Siisa form', a new genotype related to Onchocerca ochengi in cattle from North Cameroon. Acta Trop. 127(3):261-5
Eisenbarth A, Ekale D, Hildebrandt J, Achukwi MD, Streit A, Renz A.
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(2013) Nematode-derived proteins suppress proliferation and cytokine production of antigen-specific T cells via induction of cell death. PLoS One. 8(6):e68380
Hartmann W, Brenz Y, Kingsley MT, Ajonina-Ekoti I, Brattig NW, Liebau E, Breloer M.
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(2013) The ubiquitin-fold modifier 1 (Ufm1) cascade of Caenorhabditis elegans. J Biol Chem. 288(15):10661-71
Hertel P, Daniel J, Stegehake D, Vaupel H, Kailayangiri S, Gruel C, Woltersdorf C, Liebau E
