Biomechanical interactions of Schistosoma mansoni eggs with vascular endothelial cells facilitate egg extravasation

Abstract

The eggs of the parasitic blood fluke, Schistosoma, are the main drivers of the chronic pathologies associated with schistosomiasis, a disease of poverty afflicting approximately 220 million people worldwide. Eggs laid by Schistosoma mansoni in the bloodstream of the host are encapsulated by vascular endothelial cells (VECs), the first step in the migration of the egg from the blood stream into the lumen of the gut and eventual exit from the body. The biomechanics associated with encapsulation and extravasation of the egg are poorly understood. We demonstrate that S. mansoni eggs induce VECs to form two types of membrane extensions during encapsulation; filopodia that probe eggshell surfaces and intercellular nanotubes that presumably facilitate VEC communication. Encapsulation efficiency, the number of filopodia and intercellular nanotubes, and the length of these structures depend on the egg’s vitality and, to a lesser degree, its maturation state. During encapsulation, live eggs induce VEC contractility and membranous structures formation in a Rho/ROCK pathway-dependent manner. Using elastic hydrogels embedded with fluorescent microbeads as substrates to culture VECs, live eggs induce VECs to exert significantly greater contractile forces during encapsulation than dead eggs, which leads to 3D deformations on both the VEC monolayer and the flexible substrate underneath. These significant mechanical deformations cause the VEC monolayer tension to fluctuate with the eventual rupture of VEC junctions, thus facilitating egg transit out of the blood vessel. Overall, our data on the mechanical interplay between host VECs and the schistosome egg improve our understanding of how this parasite manipulates its immediate environment to maintain disease transmission.

Winners vs. losers: Schistosoma mansoni intestinal and liver eggs exhibit striking differences in gene expression and immunogenicity

“…Liver eggs have also been used to study the extravasation of eggs into intestinal tissues and the intestinal lumen. While the initial transition may be assumed to be similar for both localizations, drawn conclusions about the life cycle based solely on “losers” may not be entirely accurate [ 56 ]. The same oversight has been made by authors in recent literature attempting to elucidate the principles of egg migration in granulomas through the intestinal wall using liver-derived eggs [ 5 ].…”

Tunable photoinitiated hydrogel microspheres for direct quantification of cell-generated forces in complex three-dimensional environments

“…One of the many potential applications of hydrogel microspheres could be quantifying the contractile responses of vascular endothelial cells to transmigrating leukocytes 36,51,52 , blood flukes and their eggs 53 , or nanoparticles associated with pollution and drug delivery vectors 54 . To investigate these processes in the past, researchers used flat substrates containing fiduciary deformation markers, most often based on micropillar arrays or PAAm gels seeded with fluorescent nanobeads 55,56 .…”

Human growth factor-mediated signalling through lipid rafts regulates stem cell proliferation, development and survival of Schistosoma mansoni

“…Next, the adult male and female worms couple, mature and journey to their preferred mating sites, the mesenteric veins ( Schistosoma mansoni and S. japonicum ), or the veins surrounding the bladder ( S. haematobium ), where they lay hundreds to thousands of eggs daily for disease transmission [ 6 ]. Schistosome eggs that fail extravasation and host exit get trapped in tissues such as the gut, liver, and spleen and release immunomodulatory molecules that drive the generation of granulomas and fibrosis, pathologies associated with the disease [ 7 , 8 ].…”