Defense peptides secreted by helminth pathogens: antimicrobial and/or immunomodulator molecules?

Abstract

Host defense peptides (HDPs) are an evolutionarily conserved component of the innate immune response found in all living species. They possess antimicrobial activities against a broad range of organisms including bacteria, fungi, eukaryotic parasites, and viruses. HDPs also have the ability to enhance immune responses by acting as immunomodulators. We discovered a new family of HDPs derived from pathogenic helminth (worms) that cause enormous disease in animals and humans worldwide. The discovery of these peptides was based on their similar biochemical and functional characteristics to the human defense peptide LL-37. We propose that these new peptides modulate the immune response via molecular mimicry of mammalian HDPs thus providing a mechanism behind the anti-inflammatory properties of helminth infections.

Keywords: antimicrobial peptides; defense peptides; helminths; immunomodulation; innate immune system; parasites; trematodes.

Figure 1

(A) Primary amino acid sequence of the archetypal HDM secreted by Fasciola hepatica, FhHDM-1. The N-terminal signal peptide is shown in italics and the predicted secondary structure (predominantly alpha helix) is shown below. (B) Model structure of FhHDM-1 with the residues forming the hydrophobic face of the molecule shown in red. (C) Helical wheel analysis shows that the C-terminal region of FhHDM-1 forms a distinct amphipathic helix.