Cathelicidin-like Helminth Defence Molecules (HDMs): Absence of Cytotoxic, Anti-microbial and Anti-protozoan Activities Imply a Specific Adaptation to Immune Modulation

Karine Thivierge, Sophie Cotton, Deborah A. Schaefer, Michael W Riggs, Joyce To, Maria E. Lund, Mark W. Robinson, John P. Dalton, Sheila M. Donnelly

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere2307
JournalPLoS Neglected Tropical Diseases
Volume7
Issue number7
DOIs
StatePublished - Jul 2013

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Helminths
Peptides
Fasciola hepatica
Macrophage Activation
Schistosoma mansoni
CAP18 lipopolysaccharide-binding protein
Mammals
Sheep
Parasites
B-Lymphocytes
Erythrocytes
Macrophages
Cytokines

ASJC Scopus subject areas

  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Cathelicidin-like Helminth Defence Molecules (HDMs) : Absence of Cytotoxic, Anti-microbial and Anti-protozoan Activities Imply a Specific Adaptation to Immune Modulation. / Thivierge, Karine; Cotton, Sophie; Schaefer, Deborah A.; Riggs, Michael W; To, Joyce; Lund, Maria E.; Robinson, Mark W.; Dalton, John P.; Donnelly, Sheila M.

In: PLoS Neglected Tropical Diseases, Vol. 7, No. 7, e2307, 07.2013.

Research output: Contribution to journalArticle

Thivierge, Karine ; Cotton, Sophie ; Schaefer, Deborah A. ; Riggs, Michael W ; To, Joyce ; Lund, Maria E. ; Robinson, Mark W. ; Dalton, John P. ; Donnelly, Sheila M. / Cathelicidin-like Helminth Defence Molecules (HDMs) : Absence of Cytotoxic, Anti-microbial and Anti-protozoan Activities Imply a Specific Adaptation to Immune Modulation. In: PLoS Neglected Tropical Diseases. 2013 ; Vol. 7, No. 7.
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