Development of Acanthocheilonema viteae in Meriones shawi: Absence of microfilariae and production of active ES-62.

Development of Acanthocheilonema viteae in Meriones shawi: Absence of microfilariae and production of active ES-62.
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DOI:
10.1111/pim.12803
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发表时间:
2021-03
影响因子:
2.2
通讯作者:
Harnett W
Harnett W
中科院分区:
医学4区
文献类型:
--
作者:
Lumb FE;Doonan J;Corbet M;Pineda MA;M Harnett M;Harnett W

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ES-62是由L4-成体阶段Acanthocheilonema viteae分泌的一种经过充分研究的抗炎分子。我们使用沙鼠作为最终宿主来维持A viteae的生活周期。在这里,我们调查了是否可以维持完整的生命周期,并在相关的沙威沙鼠物种中产生功能性ES-62。蠕虫在两个物种中产生的数量相当,但在M shawi血流中观察到很少的微丝蚴(MF)。离体产生的M shawi ES-62在关节炎小鼠模型中具有功能性和保护性。比较了来自两个物种的未感染和感染沙鼠的髓源性细胞的ROS产生和破骨细胞生成,观察到两个物种在不存在和存在感染的情况下存在一些差异。A viteae的生命周期不能在M shawi jirds中成功完成,但L3阶段蠕虫发育到成年并产生功能性ES-62。对沙鼠免疫反应的初步研究表明,感染可以不同地调节这两个物种的骨髓反应。然而,需要物种特异性试剂来了解A viteae与其宿主之间的复杂相互作用,并解释感染的M shawi jirds中缺乏循环MF。
ES‐62 is a well‐studied anti‐inflammatory molecule secreted by L4‐adult stage Acanthocheilonema viteae. We maintain the life cycle of A viteae using Meriones libycus as the definitive host. Here, we investigated whether the full life cycle could be maintained, and functional ES‐62 produced, in a related jird species—Meriones shawi. Adult worms were produced in comparable numbers in the two species, but very few microfilariae (MF) were observed in the M shawi bloodstream. M shawi ES‐62 produced ex vivo was functional and protective in a mouse model of arthritis. Myeloid‐derived cells from naïve and infected jirds of both species were compared with respect to ROS production and osteoclast generation, and some differences between the two species in both the absence and presence of infection were observed. The life cycle of A viteae cannot be successfully completed in M shawi jirds but L3 stage worms develop to adulthood and produce functional ES‐62. Preliminary investigation into jird immune responses suggests that infection can differentially modulate myeloid responses in the two species. However, species‐specific reagents are required to understand the complex interplay between A viteae and its host and to explain the lack of circulating MF in infected M shawi jirds.
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