Cwiklinski, K., Jewhurst, H., McVeigh, P., Barbour, T., Maule, A., Tort, J., Robinson, M., O’Neill, S.M., Donnelly, S. & Dalton, J.P. (2018) Mol Cell Proteomics. 17:792-809. doi:10.1074/mcp.RA117.000445
Our study published in Molecular Cell Proteomics integrates a range of ‘omics’ technologies to provide a comprehensive and dynamic view of the critical processes involved in host invasion and the early stages of F. hepatica infection. We found that despite being encased in a cyst, the infective metacercariae stage is metabolically active, and primed for infection, contrary to the view that this stage is dormant. Once excysted within the mammalian host, the newly excysted juveniles (NEJ) expend vital energy stores and rapidly adjust their metabolic pathways to cope with their new and increasingly anaerobic environment. Our proteomic data revealed the major proteins secreted by the NEJ that include proteases, protease inhibitors and anti-oxidants, and an array of immunomodulators that likely disarm host innate immune effector cells. Thus, the challenges of infection by F. hepatica parasites are met by rapid metabolic and physiological adjustments that expedite tissue invasion and immune evasion. The analysis of these key parasite processes has identified key targets for future drug and vaccine strategies directed at preventing serious damage associated with acute disease.
Immunolocalization of Fasciola hepatica cathepsin L and B proteins in newly excysted juveniles by confocal scanning laser microscopy, over a 48 hour timecourse. Images represented by green fluorescence (FITC staining) within the juvenile gut.