Date Published: July 16, 2008
Publisher: Public Library of Science
Author(s): Malcolm K. Jones, Sara Lustigman, Alex Loukas, Simon Brooker
Partial Text: 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 ) swims and crawls through the snail body cavity before it burrows through a pre-formed 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 .
The first paper, by Dillon and colleagues , describes an in vitro model to explore the effects of radiation attenuation (RA) on gene expression in mechanically transformed Schistosoma mansoni cercariae. RA is a highly effective vaccine strategy, but the mechanisms of its success are not understood. Using a microarray designed to portray the transcriptome of lung-stage S. mansoni schistosomula , the authors were able to analyse global expression patterns of normal versus RA parasites at distinct time points for periods of up to 10 days, by which time the schistosomula would have migrated to the lungs. The authors demonstrated that although there are distinct differences between RA schistosomula and controls at various time points, the overriding effect of RA is that of non-specific disruption of gene expression, rather than enrichment of specific gene products. The effect of RA, then, is simply that of retarding migration and development of schistosomula, allowing time for the immune system to recognise key parasite molecules and to mount a protective response.
In a second paper, published in this issue, Hansell and colleagues  described proteomic analysis of S. mansoni cercarial secretions in human skin after cercarial penetration and transformation to schistosomula in vivo, as well as the host peptides that are present around the invading cercaria. These authors used a recently amputated limb as a model for invasion of human skin, which alone should ensure this article’s prominence in the halls of “parasitological fame”. Although the authors readily admit that postmortem changes modify aspects of the skin structure, the model does serve as a picture of early molecular interactions of the transformed cercaria and its dermal environment. Newly penetrated larvae release a gamut of proteins from the acetabular glands, including cercarial elastases, serpins, paramyosin, and glutathione-S-transferases. Some of these molecules have been already recognised as the “old guards” of immunodominant vaccine candidates . However, the present findings may help to further our understanding of the involvement of these molecules in host immune responsiveness. Other molecules released over the timeframe of analysis include tegument-associated antigens (Sm20.8) and other modulators of immune response, including a protein that belongs to the venom allergen-like protein family described for parasitic worms including the schistosomes . Hansell et al. also performed proteomic analyses of the host dermal environment around the invading cercaria.
Both contributions are inventive and demonstrate the power of combining rational experimental design with the more recently developed and available functional genomic tools to address questions related to crucial stages in establishment of schistosome infections. We now look forward to equally inventive strategies to explore other aspects of schistosome biology and development, given the complex transformation and “sojourn” of schistosomula in their mammalian hosts. The combination of these platforms, together with means for gene silencing or modification through RNAi and stable transfections , should provide substantial new information on parasite assault and host immunity. Microdissection methods will also enable analysis of the interplay within specific tissue microenvironments , particularly when coupled with transfected schistosomes expressing a fluorescent reporter . As these new areas develop, fundamental knowledge of the secretome and surface structure of cercaria, the cell biology of surface modification of transforming schistosomula, and the repertoire of interactions among secreted parasite and tissue-specific molecules of the host, would be more easily achieved.