Effect of oxygen radicals and differential expression of catalase and superoxide dismutase in adult Heligmosomoides polygyrus during primary infections in mice with differing response phenotypes

Abstract

The ability of oxygen radicals to kill Heligmosomoides polygyrus adult worms was examined by assessing parasite survival following incubation with hydrogen peroxide and acetaldehyde/xanthine oxidase, generators of H2O2 and H2O2/O2(-), respectively. H. polygyrus worms could tolerate levels of < 0.25 mM hydrogen peroxide and < 0.5 mM/20 mU acetaldehyde/xanthine oxidase for 20 h, but, at higher concentrations, marked sex-dependent susceptibility was observed, with males being more sensitive to H2O2 and O2(-) than female worms. The ability to evade free radical-mediated damage was also evaluated by measuring superoxide dismutase (SOD) and catalase levels in worms isolated at different time points from four strains of mice with differing resistance phenotypes. Levels of both catalase and SOD in female worms isolated from 'rapid'[(SWRxSJL)F1], 'fast' (SWR) or 'intermediate' (BALB/c), but not 'slow' (C57BL/10), responder mice showed a strain-dependent increase with time. Moreover, male worms were rejected faster than female worms in the 'rapid', 'fast' and 'intermediate' responder strains of mice. The results suggest that host-derived free radicals can damage adult worms and that female worms can increase production of their scavenging enzymes in response to the immune onslaught that eventually leads to worm expulsion in mice with 'fast', 'rapid' or 'intermediate' response phenotypes.

Gastrointestinal nematodes, trace elements, and immunity

“…The parasite's extensive antioxidant enzyme system, which acts to scavenge and to eradicate free radicals released by the host's MMC and leukocytes, permits it to escape their lethal effects [32,64]. The zinc metallopeptidase isolated from the luminal surface of the intestine of the sheep nematode, Haemonchus contortus, and present in E/S products is homologous with a fusion protein [27]; catalase activity has also been reported in H. contortus [65], Heligmosomoides polygyrus [66], and Necator americanus [67]. Any neutralization of these parasitic immune defense components would tip the molecular balance in favor of the host's immune response during chronic infections.…”

Quantitative trait loci for resistance to Heligmosomoides bakeri and associated immunological and pathological traits in mice: comparison of loci on chromosomes 5, 8 and 11 in F2 and F6/7 inter-cross lines of mice

“…These genes are perhaps the most likely candidates and some have plausible roles in the response to the infection. Oxygen-scavenging molecules have been shown to be differentially expressed by H. bakeri during immune responses (Ben-Smith et al 2002), and another strong responder mouse strain, SJL, generates high intestinal lumen concentrations of (Wang et al 2002). Il12 (44 .…”

Comparative Sensitivity of Feeding and Nonfeeding Stages of Heligmosomoides bakeri (Nematoda) to Boron

“…We did not determine whether boron impaired spermatogenesis in male worms, but survival data revealed that boron was more toxic to adult males than to females, as evidenced by LC 50 after 24 h and 48 h exposure. Female H. bakeri are also more resistant to oxidative attack than males (Ben-Smith et al, 2002), and these responses may have evolved as a means of ensuring prolonged egg production. Nematodes detoxify compounds such as free radicals (Hayes and Strange, 2000), toxic compounds generated in dauer larvae (McElwee et al, 2004), and heavy metals such as cadmium (Vatamaniuk et al, 2001).…”