TY - JOUR
T1 - Fasciola hepatica-Derived Molecules as Regulators of the Host Immune Response
AU - Ryan, Sinead
AU - Shiels, Jenna
AU - Taggart, Clifford C.
AU - Dalton, John P.
AU - Weldon, Sinead
PY - 2020/9/2
Y1 - 2020/9/2
N2 - 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.
AB - 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.
U2 - 10.3389/fimmu.2020.02182
DO - 10.3389/fimmu.2020.02182
M3 - Review article
VL - 11
JO - Frontiers in immunology
JF - Frontiers in immunology
SN - 1664-3224
M1 - 2182
ER -