title: 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.
authors.affiliation: Institute of Veterinary Animal and Biological Sciences, Massey University, Palmerston North, New Zealand.
authors.forename: Z U
authors.initials: ZU
authors.lastname: Rehman
authors.affiliation: The Hopkirk Research Institute, AgResearch Ltd, Palmerston North, New Zealand.
authors.forename: J S
authors.initials: JS
authors.lastname: Knight
authors.affiliation: Grasslands Research Centre, AgResearch Ltd, Palmerston North, New Zealand.
authors.forename: J
authors.initials: J
authors.lastname: Koolaard
authors.affiliation: Institute of Veterinary Animal and Biological Sciences, Massey University, Palmerston North, New Zealand.
authors.forename: H V
authors.initials: HV
authors.lastname: Simpson
authors.affiliation: The Hopkirk Research Institute, AgResearch Ltd, Palmerston North, New Zealand.
authors.forename: A
authors.initials: A
authors.lastname: Pernthaner
mesh_terms: D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology; D018925:Chemokines / Q000276:immunology*; D016207:Cytokines / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology; D006188:Haemonchiasis / Q000276:immunology*; D006189:Haemonchus / Q000276:immunology*; D006801:Humans; D007155:Immunologic Factors; D008070:Lipopolysaccharides / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D012756:Sheep
chemical_list: D000947:Antigens, Helminth; D000954:Antigens, Surface; D018925:Chemokines; D016207:Cytokines; D006684:HLA-DR Antigens; D007155:Immunologic Factors; D008070:Lipopolysaccharides
keywords: ES products; Haemonchus contortus; cytokines; immunomodulation; monocyte-derived dendritic cells; surface markers