Maruszewska-Cheruiyot Marta, Donskow-Łysoniewska Katarzyna, Piechna Karolina, Krawczak Katarzyna, Doligalska Maria
Department of Parasitology, Institute of Zoology, Faculty of Biology, University of Warsaw, Miecznikowa 1, 02-096 Warsaw, Poland.
Department of Parasitology, Institute of Zoology, Faculty of Biology, University of Warsaw, Miecznikowa 1, 02-096 Warsaw, Poland.
Exp Parasitol. 2019 Jan;196:12-21. doi: 10.1016/j.exppara.2018.10.010. Epub 2018 Nov 19.
Helminths and their products are strong candidates for the treatment of autoimmunological disorders and allergies. Being a key population of antigen-presenting cells, dendritic cells play a crucial role in the therapeutic potential of worms. The study compares the effects of live pre-male and pre-female L4 stage Heligmosomoides polygyrus administration on the maturation and activation of the JAWS II line of immature dendritic cells. On stimulation with L4 stage H. polygyrus, JAWS II cells acquire semi-mature status and induce Th2 and regulatory responses in vitro. The strongest immunosuppressive effect on JAWS II cells was observed following stimulation with both sexes of nematodes together; this was manifested as immature dendritic cell morphology, proliferation inhibition, cell cycle change, decreased translocation of NF-κB into the nucleus, and lower expression of surface cellular costimulatory molecules CD80, CD86 and MHC I. However, greater production of proinflammatory (IL-12p70, TNF-α, IL-6) and Th2 response-promoting cytokines (IL-4) was observed by JAWS II following exposure to both sexes compared to male or female larvae alone. Sex had no influence on the viability, apoptosis process or endocytosis abilities of the JAWS II cell line. The findings indicate that the presence of only a single sex of the parasite influences a developed response, resulting in reduced proinflammatory and an antiparasitic reaction.
蠕虫及其产物是治疗自身免疫性疾病和过敏症的有力候选物。作为抗原呈递细胞的关键群体,树突状细胞在蠕虫的治疗潜力中起着至关重要的作用。该研究比较了活的未成熟雄性和雌性L4期多形螺旋线虫给药对未成熟树突状细胞JAWS II系成熟和激活的影响。在用L4期多形螺旋线虫刺激后,JAWS II细胞获得半成熟状态并在体外诱导Th2和调节性反应。在用两种性别的线虫一起刺激后,观察到对JAWS II细胞的最强免疫抑制作用;这表现为未成熟树突状细胞形态、增殖抑制、细胞周期变化、NF-κB向细胞核的转位减少以及表面细胞共刺激分子CD80、CD86和MHC I的表达降低。然而,与单独暴露于雄性或雌性幼虫相比,JAWS II在暴露于两种性别后观察到促炎细胞因子(IL-12p70、TNF-α、IL-6)和促进Th2反应的细胞因子(IL-4)的产生增加。性别对JAWS II细胞系的活力、凋亡过程或内吞能力没有影响。研究结果表明,仅存在单一性别的寄生虫会影响已发展的反应,导致促炎反应和抗寄生虫反应降低。