title: Cathelicidin-like helminth defence molecules (HDMs): absence of cytotoxic, anti-microbial and anti-protozoan activities imply a specific adaptation to immune modulation.
abstract: Host defence peptides (HDPs) are expressed throughout the animal and plant kingdoms. They have multifunctional roles in the defence against infectious agents of mammals, possessing both bactericidal and immune-modulatory activities. We have identified a novel family of molecules secreted by helminth parasites (helminth defence molecules; HDMs) that exhibit similar structural and biochemical characteristics to the HDPs. Here, we have analyzed the functional activities of four HDMs derived from Schistosoma mansoni and Fasciola hepatica and compared them to human, mouse, bovine and sheep HDPs. Unlike the mammalian HDPs the helminth-derived HDMs show no antimicrobial activity and are non-cytotoxic to mammalian cells (macrophages and red blood cells). However, both the mammalian- and helminth-derived peptides suppress the activation of macrophages by microbial stimuli and alter the response of B cells to cytokine stimulation. Therefore, we hypothesise that HDMs represent a novel family of HDPs that evolved to regulate the immune responses of their mammalian hosts by retaining potent immune modulatory properties without causing deleterious cytotoxic effects.
authors.affiliation: Institute of Parasitology, McGill University, Sainte-Anne-de-Bellevue, Quebec, Canada.
authors.forename: Karine
authors.initials: K
authors.lastname: Thivierge
authors.forename: Sophie
authors.initials: S
authors.lastname: Cotton
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Schaefer
authors.forename: Michael W
authors.initials: MW
authors.lastname: Riggs
authors.forename: Joyce
authors.initials: J
authors.lastname: To
authors.forename: Maria E
authors.initials: ME
authors.lastname: Lund
authors.forename: Mark W
authors.initials: MW
authors.lastname: Robinson
authors.forename: John P
authors.initials: JP
authors.lastname: Dalton
authors.forename: Sheila M
authors.initials: SM
authors.lastname: Donnelly
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism; D023181:Antimicrobial Cationic Peptides / Q000276:immunology* / Q000378:metabolism; D001419:Bacteria / Q000187:drug effects; D002417:Cattle; D002478:Cells, Cultured; D003603:Cytotoxins / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects; D005210:Fasciola hepatica / Q000276:immunology*; D015801:Helminth Proteins / Q000276:immunology* / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology* / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D012550:Schistosoma mansoni / Q000276:immunology*; D054804:Cathelicidins
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D003603:Cytotoxins; D015801:Helminth Proteins; D007155:Immunologic Factors; D054804:Cathelicidins