Hookworm Secreted Extracellular Vesicles Interact With Host Cells and Prevent Inducible Colitis in Mice.

摘要: Gastrointestinal (GI) parasites, hookworms in particular, have evolved to cause minimal harm their hosts, allowing them establish chronic infections. This is mediated by creating an immunoregulatory environment. Indeed, are such potent suppressors of inflammation that they been used clinical trials treat inflammatory bowel diseases (IBD) and celiac disease. Since the recent description helminths (worms) secreting extracellular vesicles (EVs), exosome-like EVs from different characterized salient roles parasite-host interactions highlighted. Here, we analyze rodent parasite Nippostrongylus brasiliensis, which has as a model for human hookworm infection. N. brasiliensis (Nb-EVs) actively internalized mouse gut organoids, indicating role driving parasitism. We proteomics RNA-Seq profile molecular composition Nb-EVs. identified 81 proteins, including proteins frequently present exosomes (like tetraspanin, enolase, 14-3-3 protein, heat shock proteins), 27 sperm-coating protein-like proteins. analysis revealed 52 miRNA species, many putatively map genes involved regulation inflammation. To determine whether GI nematode had immunomodulatory properties, assessed potential suppress inducible chemical colitis. but not those whipworm Trichuris muris or control grapes protected against colitic mice received single intraperitoneal injection EVs. Key cytokines associated with pathology (IL-6, IL-1β, IFNγ, IL-17a) were significantly suppressed colon tissues EV-treated mice. By contrast, high levels anti-inflammatory cytokine IL-10 detected Nb-EV-treated Proteins miRNAs contained within helminth hold great application development drugs infections well non-infectious resulting dysregulated immune system, IBD.