Cathelicidin-like helminth defence molecules (HDMs): absence of cytotoxic, anti-microbial and anti-protozoan activities imply a specific adaptation to immune modulation

• Published in: PLoS neglected tropical diseases Vol. 7; no. 7; p. e2307
• Main Authors: Thivierge, Karine, Cotton, Sophie, Schaefer, Deborah A, Riggs, Michael W, To, Joyce, Lund, Maria E, Robinson, Mark W, Dalton, John P, Donnelly, Sheila M
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 2013; Public Library of Science (PLoS)
• Subjects: Animals; Anti-Bacterial Agents - metabolism; Antimicrobial Cationic Peptides - immunology; Antimicrobial Cationic Peptides - metabolism; Bacteria - drug effects; Biology; Cattle; Cells, Cultured; Cytokines; Cytotoxins - metabolism; Erythrocytes - drug effects; Fasciola hepatica; Fasciola hepatica - immunology; Helminth Proteins - immunology; Helminth Proteins - metabolism; Host-Pathogen Interactions; Humans; Immune system; Immunologic Factors - immunology; Immunologic Factors - metabolism; Macrophage Activation - drug effects; Macrophages - drug effects; Macrophages - immunology; Medical research; Medicine; Mice; Mice, Inbred BALB C; Parasites; Schistosoma mansoni; Schistosoma mansoni - immunology; Wound healing; Immunologic Factors; Schistosoma mansoni; Antimicrobial Cationic Peptides; Humans; Cells, Cultured; Erythrocytes; Macrophages; Macrophage Activation; Host-Pathogen Interactions; Cytotoxins; Fasciola hepatica; Anti-Bacterial Agents; Animals; Helminth Proteins; Cattle; Bacteria; Mice; Mice, Inbred BALB C
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0002307

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.