Toxocara canis: genes expressed by the arrested infective larval stage of a parasitic nematode

Abstract

Toxocara canis is a widely distributed nematode parasite which reaches maturity in dogs. However, eggs voided by canid animals are infective to a very wide range of paratenic hosts including humans. In noncanid hosts, infective larvae emerge from the eggs and invade the soft tissues, often entering the brain and musculature. Such larvae may remain for many months or years in these tissues without further growth or differentiation, and yet appear to evade inflammatory reactions or other modes of immune attack. To understand the ability of T. canis larvae to survive in the immunocompetent host, we have undertaken a molecular analysis of the major genes expressed at this stage. By a combination of protein sequencing, gene identification, and expressed sequence tag (EST) analysis we have characterised a range of potentially important gene products from this parasite. Some of these are homologues of prominent mammalian proteins such as C-type lectins (represented by the secreted products TES-32 and TES-70), and mucins (TES-120), and additional products show strong similarities to known cysteine proteases, phosphatidylethanolamine-binding proteins and other ligands. A number of these proteins include a conspicuous 36-amino acid motif containing six cysteines. This domain (termed NC6 or SXC) appears to be an evolutionarily mobile module, which in T. canis is combined with a spectrum of diverse functional domains in different genes. In addition, we have identified a set of novel gene sequences that show no resemblance to any genes encoded by the free-living nematode C. elegans. Four of these are designated abundant novel transcripts, and collectively these account for nearly 20% of the cDNA isolated from the arrested infective stage. Such parasite-specific genes expressed at a high level by a stage that shows remarkable endurance may represent critical products necessary for the success of the parasitic mode of life.