Glutathione S-transferase (GST) expression in the human hookworm Necator americanus: potential roles for excretory-secretory forms of GST

Abstract

The difficulty in demonstrating protective immunity to human gastro-intestinal nematodes is thought to be a consequence of the expression of defences by the parasites directed against the toxic metabolites of leukocytes produced during inflammation (Brophy and Pritchard, 1992a). Parasite glutathione S-transferases (GSTs) may provide part of this defence by detoxifying the secondary products of lipid peroxidation produced via immune initiated free-radical attack on host or parasite membranes (Brophy and Pritchard, 1994; Taylor et al., 1988). Neutralisation of parasite immune defence components could tip the molecular balance in favour of the immune response during chronic infections. For example, GSTs have been extensively investigated from the digenean parasites Schistosoma and Fasciola hepatica and provide protection in animal-model systems (Mitchell, 1988; Wijffels et al., 1991). In contrast, although GSTs have been initially characterised in filarial nematodes (Salinas et al., 1994; Leibau et al., 1994; Jaffe and Lambert, 1986), there is limited information on GSTs from human gastro-intestinal nematode parasites. We were particularly interested in analysing the products of hookworms for evidence of the presence of excretory-secretory forms of this putative immune defence protein.