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犬弓首蛔虫幼虫排泄/分泌蛋白损害了嗜酸性粒细胞依赖的小鼠对巴西日圆线虫的抵抗能力。

Toxocara canis larval excretory/secretory proteins impair eosinophil-dependent resistance of mice to Nippostrongylus brasiliensis.

机构信息

School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia, Australia.

出版信息

Parasite Immunol. 2008 Aug;30(8):435-45. doi: 10.1111/j.1365-3024.2008.01040.x.

Abstract

Survival of parasitic helminths within a host requires immune evasion and excretory/secretory (ES) proteins may contribute to this process. Eosinophils are important effector cells in immunity of mice to the nematode Nippostrongylus brasiliensis and eosinophilic interleukin-5 transgenic (IL-5 Tg) mice are highly resistant to the earliest stages of primary infections. In contrast, Toxocara canis is largely resistant to eosinophils, with viable larvae encysted in tissues often surrounded by these and other leucocytes. The aim of this study was to investigate whether T. canis ES (TES) proteins inhibit eosinophil-dependent resistance to N. brasiliensis. Mouse serum pre-treated with TES had reduced capacity to mediate the adherence of leucocytes to N. brasiliensis infective-stage larvae (L3) and this correlated with reduced complement C3 deposition on the parasite. TES did not inhibit eosinophil survival or eotaxin-dependent eosinophil migration in vitro. Cellular inflammation and eosinophil degranulation in the skin in response to injection of L3 was also not impaired by TES. However, when TES was included with L3 in an inoculum given to IL-5 Tg mice, a greatly increased number of parasites migrated to the lung. This suggests that the early eosinophil-dependent resistance in these mice was suppressed, by mechanisms yet to be determined.

摘要

寄生虫在宿主体内的生存需要免疫逃避,而排泄/分泌(ES)蛋白可能有助于这一过程。嗜酸性粒细胞是小鼠对旋毛虫(Nippostrongylus brasiliensis)免疫的重要效应细胞,而嗜酸性白细胞介素-5 转基因(IL-5 Tg)小鼠对原发性感染的早期阶段具有高度抗性。相比之下,犬弓首蛔虫对嗜酸性粒细胞有很大的抵抗力,活幼虫囊包在组织中,通常被这些和其他白细胞包围。本研究旨在探讨犬弓首蛔虫 ES(TES)蛋白是否抑制嗜酸性粒细胞依赖的对旋毛虫的抗性。用 TES 预处理的小鼠血清降低了白细胞与旋毛虫感染期幼虫(L3)结合的能力,这与寄生虫上补体 C3 沉积减少有关。TES 不抑制嗜酸性粒细胞的存活或嗜酸性粒细胞趋化因子依赖性迁移。在注射 L3 后,皮肤中的细胞炎症和嗜酸性粒细胞脱颗粒也没有被 TES 损害。然而,当 TES 与 L3 一起包含在接种物中给予 IL-5 Tg 小鼠时,大量寄生虫迁移到肺部。这表明这些小鼠的早期嗜酸性粒细胞依赖性抗性受到抑制,具体机制尚待确定。

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