title: Excretory/secretory products of adult Haemonchus contortus and Teladorsagia circumcincta which increase the permeability of Caco-2 cell monolayers are neutralised by antibodies from immune hosts.
abstract: The onset of abomasal pathophysiology due to parasitism coincides with the presence of adult worms in the lumen, implicating worm excretory/secretory (ES) products acting on the surface mucosa. Caco-2 cell monolayers were grown to confluence on Transwell plates and exposed on the apical side to ES products of adult Haemonchus contortus and Teladorsagia circumcincta. ES products of both species significantly (p<0.001) reduced transepithelial electrical resistance after 2h to 81.1±1.0% and 82.9±1.1% respectively. Immunocytochemical staining of the Caco-2 monolayers for zona occludens-1 and occludin confirmed that the tight junctions remained intact in control medium, but these proteins were internalised from disrupted junctions after exposure to ES products. The components of H. contortus ES products responsible for increased epithelial permeability were partially blocked by phage displaying single chain antibodies derived from sheep immune to field infection and enriched by panning with H. contortus ES products. Immune hosts may therefore be able to reduce the effects of worm chemicals on the gastric epithelium. Permeabilisation of the abomasal surface mucosa by worm chemicals would also explain how cells deep in the gastric glands could rapidly be affected by parasites emerging from the glands or within a day of transplantation of adult worms into naïve hosts, resulting in the pathophysiology typically caused by abomasal nematode parasitism.
authors.affiliation: Institute of Veterinary, Animal and Biomedical Sciences, Massey University, Private Bag 11-222, Palmerston North, New Zealand.
authors.forename: Z U
authors.initials: ZU
authors.lastname: Rehman
authors.affiliation: AgResearch Ltd., Private Bag 11-008, Palmerston North, New Zealand.
authors.forename: Q
authors.initials: Q
authors.lastname: Deng
authors.affiliation: AgResearch Ltd., Private Bag 11-008, Palmerston North, New Zealand.
authors.forename: S
authors.initials: S
authors.lastname: Umair
authors.affiliation: Institute of Fundamental Sciences, Massey University, Private Bag 11-222, Palmerston North, New Zealand.
authors.forename: M S
authors.initials: MS
authors.lastname: Savoian
authors.affiliation: AgResearch Ltd., Private Bag 11-008, Palmerston North, New Zealand.
authors.forename: J S
authors.initials: JS
authors.lastname: Knight
authors.affiliation: AgResearch Ltd., Private Bag 11-008, Palmerston North, New Zealand.
authors.forename: A
authors.initials: A
authors.lastname: Pernthaner
authors.affiliation: Institute of Veterinary, Animal and Biomedical Sciences, Massey University, Private Bag 11-222, Palmerston North, New Zealand. Electronic address: H.V.Simpson@massey.ac.nz.
authors.forename: H V
authors.initials: HV
authors.lastname: Simpson
mesh_terms: D000818:Animals; D000909:Antibodies, Helminth / Q000378:metabolism*; D057134:Antibodies, Neutralizing / Q000378:metabolism*; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability / Q000187:drug effects; D006189:Haemonchus / Q000737:chemistry / Q000502:physiology*; D015801:Helminth Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D006790:Host-Parasite Interactions / Q000502:physiology*; D006801:Humans
chemical_list: D000909:Antibodies, Helminth; D057134:Antibodies, Neutralizing; D015801:Helminth Proteins
keywords: Caco-2 cell TEER; ES products; Epithelial permeability; Haemonchus contortus; Phage display; Single chain antibodies; Teladorsagia circumcincta