Unaltered influenza disease outcomes in swine prophylactically treated with α-galactosylceramide.

Unaltered influenza disease outcomes in swine prophylactically treated with α-galactosylceramide.
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DOI:
10.1016/j.dci.2020.103843
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发表时间:
2021-01
影响因子:
2.9
通讯作者:
Driver JP
Driver JP
中科院分区:
生物学3区
文献类型:
--
作者:
Gu W;Madrid DMD;Yang G;Artiaga BL;Loeb JC;Castleman WL;Richt JA;Lednicky JA;Driver JP

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甲型流感病毒 (IAV) 是猪呼吸道疾病的主要原因。不变自然杀伤 T (iNKT) 细胞是一种先天性 T 细胞亚群,对小鼠 IAV 耐药性有显着贡献。在当前的工作中,我们探讨了使用 iNKT 细胞超级激动剂 α-半乳糖神经酰胺 (α-GalCer) 扩增和激活 iNKT 细胞是否会改变猪 IAV 感染的过程。在一项研究中,在感染前 9 天给猪肌内注射 α-GalCer,从而系统性地扩增 iNKT 细胞。在另一项研究中,在病毒感染前 2 天鼻内 (i.n.) 施用 α-GalCer 以激活粘膜 iNKT 细胞。尽管当 α-GalCer 肌内注射时,iNKT 细胞会协同增加。接受治疗的猪感染了 IAV,但这两种方法都没有减少疾病症状、肺部病理或病毒复制。我们的结果表明,预防性使用 iNKT 细胞激动剂来预防 IAV 感染对猪是无效的。这很重要,因为这种方法已被考虑用于人类,其 iNKT 细胞水平和 IAV 感染与猪比小鼠更相似。
Influenza A viruses (IAV) are a major cause of respiratory diseases in pigs. Invariant natural killer T (iNKT) cells are an innate-like T cell subset that contribute significantly to IAV resistance in mice. In the current work, we explored whether expanding and activating iNKT cells with the iNKT cell superagonists α-galactosylceramide (α-GalCer) would change the course of an IAV infection in pigs. In one study, α-GalCer was administered to pigs intramuscularly (i.m.) 9 days before infection, which systemically expanded iNKT cells. In another study, α-GalCer was administered intranasally (i.n.) 2 days before virus infection to activate mucosal iNKT cells. Despite a synergistic increase in iNKT cells when α-GalCer i.m. treated pigs were infected with IAV, neither approach reduced disease signs, lung pathology, or virus replication. Our results indicate that prophylactic use of iNKT cell agonists to prevent IAV infection is ineffective in pigs. This is significant because this type of approach has been considered for humans whose iNKT cell levels and IAV infections are more similar to those of pigs than mice.
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