Tracking the Odysseys of Juvenile Schistosomes to Understand Host Interactions

The prospects confronting a ‘‘new-born’’ schistosome cercaria are formidable. That some of these microscopic helminths successfully negotiate the tortuous route from snail to human vasculature is a truly remarkable feature of adaptive biology. After escaping the birth pore of its parental sporocyst, a cercaria (at least we infer from studies of other digeneans [1]) swims and crawls through the snail body cavity before it burrows through a preformed escape tunnel to the aquatic environment. Once in that milieu, a cyclical suite of swimming behaviours positions the cercaria for its potential assault on the skin of an available host, should one appear. Upon skin penetration, the larva (now called a schistosomulum) sits within the skin for up to 72 hours before tracking to the lung, whereupon it re-enters a second static phase. This journey takes the organism through three distinct environments (five if we include the solid integuments of snail and human hosts), incorporates a wholesale remodelling of the surface membrane, and includes two poorly understood periods of relative immobility in the skin and the lung. Further development in the liver is required before the adults reach their ultimate destination in the vasculature of the intestine or bladder. How the juvenile stages of schistosomes negotiate these environments is of intense interest, not the least because protective immunity in schistosome infections, when it occurs, appears to be directed against the early intra-host stages, with the principal target being the lung stage schistosomulum [2]. There is much to be learnt about the first few weeks of cercarial establishment in the human host, but a detailed picture of the molecular and cellular events during this time has been difficult to obtain. The limitations arise partly because of the difficulties in accessing material from experimental or natural infection, and past technological limitations. Despite major advances in our understanding of parasite transformation (reviewed recently in [3]), and of the host–parasite interplay in early establishment [4], there remain many questions, the answers to which will undoubtedly guide discovery of novel targets for drugs and vaccines. Some of the questions that are still unanswered are: