Oral Presentation Australasian Extracellular Vesicles Conference 2018

Extracellular vesicles from hookworms and their therapeutic potential (#22)

Ramon M Eichenberger 1 , Javier Sotillo 1 , Alex Loukas 1
  1. Centre for Biodiscovery and Molecular Development of Therapeutics, AITHM, James Cook University, Cairns, QLD, Australia

Helminth parasites (parasitic worms) have evolved a vast array of strategies to manipulate their vertebrate hosts. Extracellular vesicles (EVs) are secreted by all helminth species investigated thus far, and their salient roles in parasite–host interactions are being revealed. Adult hookworms live in the intestine of the host where they release excretory/secretory products, representing the major host-parasite interface. While studies on parasite-host interactions have traditionally focused on soluble proteins, we focus herein on the characterization of secreted extracellular vesicles (EVs). Here, we analyse EVs from the rodent parasite Nippostrongylus brasiliensis, which has been used as a model for human hookworm infection, and used proteomics and RNA Seq to profile the molecular composition of N. brasiliensis EVs. Helminths manipulate the host’s immune system towards an immunoregulatory phenotype, which can have beneficial effects for both the parasite and the host. Consequently, there is interest in harnessing the immunoregulatory capabilities of helminths and their secreted products for the development of novel therapies for autoimmune, allergic and even metabolic diseases. Indeed, we have shown that hookworm EVs confer protection against inflammation in models of acute and chronic colitis, and moreover, hookworm EVs contain miRNAs that are predicted to bind to murine genes with known roles in driving colitis. Helminth EVs and EV proteins are also of interest as candidates for innovative anthelmintic vaccines, and we have begun to evaluate their protective capacity against hookworm challenge infection. Our studies will reveal potential applications in helminth drug development and vaccine design, as well as development of an entirely new generation of therapeutics to treat chronic non-infectious diseases.