Schistosoma mansoni-derived lipids in extracellular vesicles: Potential agonists for eosinophillic tissue repair

Abstract

The co-evolution of helminths with their hosts has required these parasites to develop a range of sophisticated molecular mechanisms and adaptations to evade, suppress and activate host cells to maximize survival and maintain infection within their chosen niche. Recent studies have revealed that Schistosoma mansoni (S. mansoni)-derived lipids are agonists of innate pattern recognition receptors on eosinophils, mediating a pro-fibrotic phenotype. Indeed, the release of lipids from Schistosoma could be a key factor driving disease pathogenesis in hepatosplenic forms of the infection, where excessive hepatic fibrosis is linked to significant morbidity. A fundamental question that remains is how are lipids derived from the tegumental outer surface of S. mansoni adult worms, cercariae and eggs, transported and protected from the inflammatory milieu to target and activate surface receptors on eosinophils. The recent identification of lipid-enriched extracellular vesicles (EVs) as an evolutionarily conserved form of host-pathogen communication, has led us to speculate that S. mansoni-derived extracellular vesicles are responsible for the targeting of bioactive lipids to eosinophils, and we argue that these cargo delivery systems may be an influential factor in both tissue repair and fibrosis during helminth infection.