Immunomodulatory effects of adult Haemonchus contortus excretory/secretory products on human monocyte‐derived dendritic cells

Abstract

The levels of expression of surface molecules and release of cytokines and chemokines of human monocyte-derived dendritic cells were determined after their exposure to adult H. contortus excretory/secretory (ES) products or a combination of ES products and bacterial lipopolysaccharide (LPS). Worm products provoked a weak response and only partial maturation of the dendritic cells, consistent with the hyporesponsiveness and more tolerogenic immune environment present in parasitized animals and humans. Co-stimulation with LPS demonstrated that H. contortus secretions, like those of other helminths, contain immunomodulators capable of reducing some aspects of the strong T(H)1/T(H)2 response evoked by bacterial LPS. There were significant reductions in the release of some cytokine/chemokines by LPS-stimulated mdDCs and a trend (although not significant at P < 0.05) for reduced expression levels of CD40, CD80 and HLA-DR. A prominent feature was the variability in responses of dendritic cells from the four donors, even on different days in repeat experiments, suggesting that generalized conclusions may be difficult to make, except in genetically related animals. Such observations may therefore be applicable only to restricted populations. In addition, previous exposure to parasites in a target population for immunomodulatory therapy may be an important factor in assessing the likelihood of adverse reactions or failures in the treatment to worm therapy.

The excretory/secretory products of fifth-stage larval Angiostrongylus cantonensis induces autophagy via the Sonic hedgehog pathway in mouse brain astrocytes

“…During parasitic helminth infection, parasites, including Angiostrongylus cantonensis, Ancylostoma caninum, hookworm, Trichinella spiralis, Trichuris suis, Haemonchus contortus, Anisakis pegreffii and Contracaecum osculatum, can produce excretory-secretory products (ESPs) to modulate the host response [33,[37][38][39][40][41][42][43]. ESPs play an important role in the interaction between parasites and hosts and are essential factors for host tissue invasion, digestion, feeding, development, molting, host immune responses, oxidative stress, and apoptosis [40,44].…”

The lipid composition of the exo-metabolome from Haemonchus contortus

“…Helminths such as H. contortus secrete several biological particles, termed parasite-derived biomolecules (PDBMs), exhibiting different properties [6][7]. Among the PDBMs, the protein content secreted by parasitic nematodes, known as excretory-secretory products (ESPs), have been extensively studied regarding their interaction with the host immune system [8][9][10][11]. However, the range of PDBMs is broad.…”

Targeting the nervous system of the parasitic worm, Haemonchus contortus with quercetin

“…Due to its blood-feeding behavior and the potential for the rapid development of large burdens, it is a frequent cause of mortalities in sheep, cattle, goats, and other ruminants as well as is the most important parasite of the livestock in the warm climatic regions, and arguably on a global basis 20,21 . Importantly, multiple reports of infections from different continents with H. contortus have raised serious veterinary concerns while considering the development of resistance in this parasite against the available anthelmintic drugs [22][23][24][25] . Anthelminthic resistance is now a widespread problem, especially in H. contortus, due to its enormous genetic diversity, which possibly is allowing the anthelminthic resistance alleles to be rapidly selected 26,27 .…”