IL-17A regulates Eimeria tenella schizont maturation and migration in avian coccidiosis.

IL-17A regulates Eimeria tenella schizont maturation and migration in avian coccidiosis.
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DOI:
10.1186/1297-9716-45-25
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发表时间:
2014-02-26
影响因子:
4.4
通讯作者:
Sánchez-Acedo C
Sánchez-Acedo C
中科院分区:
农林科学2区
文献类型:
--
作者:
Del Cacho E;Gallego M;Lillehoj HS;Quílez J;Lillehoj EP;Ramo A;Sánchez-Acedo C

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尽管 IL17A 与多种传染病的免疫控制有关,但其在宿主对艾美耳球虫感染反应中的作用尚不清楚。为了更好地剖析 IL17A 在禽球虫病宿主-病原体相互作用中的作用,使用鸡 IL17A 的中和抗体 (Ab) 来抵消 IL17A 体内的生物活性。感染柔嫩艾美耳球虫并用 IL17A Ab 静脉注射处理的鸡与未处理的对照相比,表现出细胞内裂殖体和裂殖子发育减少,病变评分减少。对寄生组织中盲肠病变的免疫组织学评估表明,第二代裂殖体的迁移和成熟减少,固有层和粘膜下层病变减少。相比之下,未经治疗和感染的鸡的上皮细胞含有第二代裂殖体,这些裂殖体通过粘膜肌层破坏延伸到粘膜下层,成熟为第二代裂殖子。此外,IL17A Ab 治疗与 Th1 免疫参数(产生 IL2 和 IFNγ 的细胞)增加、活性氧 (ROS) 水平降低以及血清基质金属蛋白酶 9 (MMP-9) 水平降低相关。最后,未处理和感染鸡的裂殖体在裂殖子成熟时表达 S100、Wiskott-Aldrich 综合征蛋白家族成员 3 (WASF3) 和热休克蛋白 70 (HSP70) 蛋白,而这些蛋白在 IL17A Ab 处理的鸡中不表达。这些结果提供了第一个证据,表明对柔嫩球虫感染的鸡施用IL17A中和抗体可抑制寄生上皮细胞的迁移,显着减少ROS和MMP-9的产生,并减少盲肠病变,表明IL17A可能是控制球虫病的潜在治疗靶点。
Although IL17A is associated with the immunological control of various infectious diseases, its role in host response to Eimeria infections is not well understood. In an effort to better dissect the role of IL17A in host-pathogen interactions in avian coccidiosis, a neutralizing antibody (Ab) to chicken IL17A was used to counteract IL17A bioactivity in vivo. Chickens infected with Eimeria tenella and treated intravenously with IL17A Ab, exhibited reduced intracellular schizont and merozoite development, diminished lesion score, compared with untreated controls. Immunohistological evaluation of cecal lesions in the parasitized tissues indicated reduced migration and maturation of second-generation schizonts and reduced lesions in lamina propria and submucosa. In contrast, untreated and infected chickens had epithelial cells harboring second-generation schizonts, which extend into the submucosa through muscularis mucosa disruptions, maturing into second generation merozoites. Furthermore, IL17A Ab treatment was associated with increased parameters of Th1 immunity (IL2- and IFNγ- producing cells), reduced levels of reactive oxygen species (ROS), and diminished levels of serum matrix metalloproteinase-9 (MMP-9). Finally, schizonts from untreated and infected chickens expressed S100, Wiskott-Aldrich syndrome protein family member 3 (WASF3), and heat shock protein-70 (HSP70) proteins as merozoites matured, whereas the expression of these proteins was absent in IL17A Ab-treated chickens. These results provide the first evidence that the administration of an IL17A neutralizing Ab to E. tenella-infected chickens inhibits the migration of parasitized epithelial cells, markedly reduces the production of ROS and MMP-9, and decreases cecal lesions, suggesting that IL17A might be a potential therapeutic target for coccidiosis control.
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