Authors

Discussion

The outer surface tegument layer of schistosomes is thought to be vital for schistosome survival in the mammalian host. However, the importance of this unique organ to schistosome growth and development, and how it interfaces with host molecules to support these processes, is not well understood. Across several projects, we have sought to elucidate how lipid rafts, important cholesterol-rich membrane microdomains, act as cellular signalling hubs in Schistosoma mansoni, and how such signalling drives the growth, development, and survival of the parasite, particularly the exponentially growing liver schistosomula stage. We demonstrate that lipid rafts cluster in response to human epidermal growth factor (EGF) in schistosomula, concomitant with the localisation of receptors that bind human EGF (EGFRs) and insulin (IRs). The activation of several protein kinase pathways within the parasite, including protein kinase C (PKC), extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38 MAPK), and Akt were modulated by tegument cholesterol depletion, with effects reversed by cholesterol reloading. We also demonstrate that heat shock protein 90 (HSP90) acts as an important signalling hub to these protein kinases in schistosomes. Lipid raft disruption or blockade of EGFR signalling at the tegument surface reduced somule motility and survival, and blunted stem cell proliferation and somule growth and development, particularly to the liver schistosomula stage. Our findings support a novel paradigm for schistosome growth and vitality in the human host, directed by tegument associated host-parasite interactions, that could be exploitable for developing of new approaches for schistosomiasis control.