Secreted Proteins, Infectivity and Immunity to the Parasitic Nematode Nippostrongylus brasiliensis

Abstract

Comparative analysis of a recent isolate (J) and a laboratory-adapted strain (W) of the parasitic nematode Nippostrongylus brasiliensis found that the former had higher fecundity and gave rise to more persistent infections, although these traits were partially abolished after three years of laboratory passage, suggesting that infection dynamics can be modified by continuous high-dose propagation. Host immune responses to the two strains were similar in mode and magnitude. Proteins secreted by infective larvae (L3) and adult parasites showed some subtle differences between strains, although the activity of enzymes which might impact on persistence such as acetylcholinesterases and nucleotide metabolising enzymes were similar. Activation of N. brasiliensis L3 was not influenced by host serum, but a 37°C temperature cue was sufficient to induce feeding and protein secretion. Rat skin extracts induced chemotaxis of L3 and also induced the secretion of pre-synthesised proteins, although feeding and subsequent protein secretion were unaffected. Analysis of L3 secreted products by two-dimensional immunoblotting revealed differential immune recognition of specific proteins. Analysis of host resistin-like molecules showed that they had no effect on parasite chemotaxis and feeding activities, in contrast to published data. The venom-allergen homologue/ASP-like (VAL) proteins are important therapeutic targets found in all parasitic nematodes studied to date, and eight secreted variants of VALs have been discovered in N. brasiliensis. Although N. brasiliensis VALs (NbVALs) were found to be immunogenic during natural infection, immunisation with recombinant NbVAL-7 did not protect mice against challenge. Moreover, natural infection induced antigen-specific IgE and Type I hypersensitivity reactions to NbVALs, suggesting that this may be an intrinsic property of these proteins which limits their use in immunoprophylaxis of nematode infection.