Fasciola hepatica-Derived Molecules as Regulators of the Host Immune Response

Front Immunol. 2020 Sep 2;11:2182. doi: 10.3389/fimmu.2020.02182. eCollection 2020.

Abstract

Helminths (worms) are one of the most successful organisms in nature given their ability to infect millions of humans and animals worldwide. Their success can be attributed to their ability to modulate the host immune response for their own benefit by releasing excretory-secretory (ES) products. Accordingly, ES products have been lauded as a potential source of immunomodulators/biotherapeutics for an array of inflammatory diseases. However, there is a significant lack of knowledge regarding the specific interactions between these products and cells of the immune response. Many different compounds have been identified within the helminth "secretome," including antioxidants, proteases, mucin-like peptides, as well as helminth defense molecules (HDMs), each with unique influences on the host inflammatory response. HDMs are a conserved group of proteins initially discovered in the secretome of the liver fluke, Fasciola hepatica. HDMs interact with cell membranes without cytotoxic effects and do not exert antimicrobial activity, suggesting that these peptides evolved specifically for immunomodulatory purposes. A peptide generated from the HDM sequence, termed FhHDM-1, has shown extensive anti-inflammatory abilities in clinically relevant models of diseases such as diabetes, multiple sclerosis, asthma, and acute lung injury, offering hope for the development of a new class of therapeutics. In this review, the current knowledge of host immunomodulation by a range of F. hepatica ES products, particularly FhHDM-1, will be discussed. Immune regulators, including HDMs, have been identified from other helminths and will also be outlined to broaden our understanding of the variety of effects these potent molecules exert on immune cells.

Keywords: Fasciola; FhHDM-1; helminth; helminth defense molecule; immunomodulation; parasite.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antigens, Helminth / immunology
  • Conserved Sequence
  • Fasciola hepatica / immunology*
  • Fascioliasis / immunology*
  • Fascioliasis / veterinary
  • Helminth Proteins / immunology*
  • Host-Pathogen Interactions / immunology*
  • Humans
  • Immune Evasion / immunology*
  • Immunity
  • Immunomodulation
  • Mice
  • Pore Forming Cytotoxic Proteins / immunology
  • Species Specificity

Substances

  • Antigens, Helminth
  • Helminth Proteins
  • Pore Forming Cytotoxic Proteins