Objective Filarial nematodes of man, like most helminth parasites, are long-lived organisms which persist in the mammalian host despite a vigorous and sustained immune response. The ability to neutralize or subvert host immunity is thus crucial to their survival. Characterization of parasite molecules involved in this process and dissection of the associated mechanisms will not only provide a focal point for the development of chemotherapy and immunoprophylaxis against filariasis, but will also provide basic information on immune effector mechanisms against complex multicellular parasites. We intend to focus upon anti-oxidant enzymes, which we propose are a primary line of defence against host immunity and the project will include studies on the three major filarial nematode parasites of man: onchocerca volvulus, Wuchereria bancrofti and Brugia malayi. We will complete the characterization of the genes for glutathione peroxidase (GSHPX) and superoxide dismutase (SOD) from 0. volvulus and Brugia, determine whether these encode distinct cytosolic and secreted enzymes and define (where possible) their expression in different stages. We will then develop antibody reagents to expressed gene products and utilize these to determine the localization of the native enzymes in different stages via immuno-electronmicroscopy. Enzyme secretion will be monitored in vivo with these reagents, and measured both biochemically and immunologically in vitro. The immune response to anti-oxidants will be assessed in Indian patients infected with W. bancrofti, most specifically by measuring antibodies which inhibit and/or bind parasite enzymes. The putative protective role of these enzymes against damage and killing by reactive oxygen metabolites will be assessed in vitro, primarily with different stages of B. malayi, by measuring the extent and site of lipid peroxidation in relation to the activity of parasite anti-oxidants. Particular attention will be focused upon the cuticle, and freeze fracture analysis will be employed to assess immune-mediated damage to cuticular membrane structures. The effect of enzyme inhibitors and inhibitory antibodies will also be determined, which will define the suitability of these molecules as targets oE chemo- or immuno-prophylaxis. Fields of science medical and health sciencesbasic medicineimmunologynatural sciencesbiological sciencesbiochemistrybiomoleculeslipidsnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Programme(s) FP3-STD 3 - Specific research and technological development programme (EEC) in the field of the life sciences and technologies for developing countries, 1990-1994 Topic(s) Data not available Call for proposal Data not available Funding Scheme CSC - Cost-sharing contracts Coordinator Bernhard Nocht Institut für Schiffs- und Tropenkrankheiten Address Bernhard-nocht-straße 74 20359 Hamburg Germany See on map EU contribution € 0,00 Participants (2) Sort alphabetically Sort by EU Contribution Expand all Collapse all Banaras Hindu University India EU contribution € 0,00 Address 221005 Varanasi - utta pradesh See on map IMPERIAL COLLEGE OF SCIENCE, TECHNOLOGY AND MEDICINE United Kingdom EU contribution € 0,00 Address SW7 2AY London See on map
