γδ T Cells Play a Protective Role in Chikungunya Virus-Induced Disease

γδ T Cells Play a Protective Role in Chikungunya Virus-Induced Disease
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DOI:
10.1128/jvi.02159-15
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发表时间:
2016-01-01
影响因子:
5.4
通讯作者:
Heise, Mark T.
Heise, Mark T.
中科院分区:
医学2区
文献类型:
--
作者:
Long, Kristin M.;Ferris, Martin T.;Heise, Mark T.

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基孔肯雅病毒(CHIKV)是一种甲病毒,可引起人类多关节痛的流行性爆发。由于CHIKV最初是通过皮肤引入的,其中γ δ T细胞是普遍存在的,因此我们评估了这些细胞对CHIKV感染的反应。CHIKV感染导致感染足和引流淋巴结中的γ δ T细胞显著增加,这与C57 BL/6 J小鼠中促炎细胞因子和趋化因子的产生相关。γ δ T细胞/小鼠表现出恶化的CHIKV疾病,其特征在于比野生型(-/-)小鼠中发生的更少的体重增加和更大的足部肿胀,以及足部中单核细胞的瞬时增加和改变的细胞因子/趋化因子表达。在组织学上,与野生型小鼠相比,γ δ T细胞(-/-)小鼠在同侧足和踝关节中具有增加的炎症介导的氧化损伤,这与CHIKV复制的差异无关。这些结果表明,γ δ T细胞在限制CHIKV诱导的炎症反应和随后的组织和关节损伤中发挥保护作用。
Chikungunya virus (CHIKV) is an alphavirus responsible for causing epidemic outbreaks of polyarthralgia in humans. Because CHIKV is initially introduced via the skin, where gamma delta T cells are prevalent, we evaluated the response of these cells to CHIKV infection. CHIKV infection led to a significant increase in gamma delta T cells in the infected foot and draining lymph node that was associated with the production of proinflammatory cytokines and chemokines in C57BL/6J mice. gamma delta T cell / mice demonstrated exacerbated CHIKV disease characterized by less weight gain and greater foot swelling than occurred in wild-type(-/-) mice, as well as a transient increase in monocytes and altered cytokine/chemokine expression in the foot. Histologically, gamma delta T cell(-/-) mice had increased inflammation-mediated oxidative damage in the ipsilateral foot and ankle joint compared to wild-type mice which was independent of differences in CHIKV replication. These results suggest that gamma delta T cells play a protective role in limiting the CHIKV-induced inflammatory response and subsequent tissue and joint damage.