Rehman Z U, Deng Q, Umair S, Savoian M S, Knight J S, Pernthaner A, Simpson H V
Institute of Veterinary, Animal and Biomedical Sciences, Massey University, Private Bag 11-222, Palmerston North, New Zealand.
AgResearch Ltd., Private Bag 11-008, Palmerston North, New Zealand.
Vet Parasitol. 2016 May 15;221:104-10. doi: 10.1016/j.vetpar.2016.03.017. Epub 2016 Mar 21.
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.
由于寄生虫感染导致的皱胃病理生理学发作与成虫在管腔内的存在同时发生，这表明蠕虫排泄/分泌（ES）产物作用于表面粘膜。将Caco-2细胞单层培养至在Transwell板上汇合，并在顶侧暴露于成年捻转血矛线虫和环形泰勒虫的ES产物。两种物种的ES产物在2小时后均显著（p<0.001）降低了跨上皮电阻，分别降至81.1±1.0%和82.9±1.1%。对Caco-2单层进行紧密连接蛋白-1和闭合蛋白的免疫细胞化学染色证实，在对照培养基中紧密连接保持完整，但在暴露于ES产物后，这些蛋白质从破坏的连接中内化。来自对野外感染具有免疫力的绵羊的噬菌体展示单链抗体部分阻断了捻转血矛线虫ES产物中负责增加上皮通透性的成分，并且通过用捻转血矛线虫ES产物淘选而富集。因此，免疫宿主可能能够减少蠕虫化学物质对胃上皮的影响。蠕虫化学物质使皱胃表面粘膜通透性增加，这也可以解释胃腺深处的细胞如何能够迅速受到从腺体中出现的寄生虫或在将成虫移植到未感染宿主后一天内的影响，从而导致通常由皱胃线虫寄生引起的病理生理学。
