γδ T Cells Provide Protective Function in Highly Pathogenic Avian H5N1 Influenza A Virus Infection
γδ T Cells Provide Protective Function in Highly Pathogenic Avian H5N1 Influenza A Virus Infection
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DOI：
10.3389/fimmu.2018.02812
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发表时间：
2018-12-04
影响因子：
7.3
通讯作者：
He, Wei
中科院分区：
文献类型：
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作者：
Dong, Peng;Ju, Xiangwu;He, Wei
高致病性禽流感（H5 N1）的高死亡率（>50%）和潜在的人际传播危险，仍然对人类构成重大威胁。参与宿主免疫防御前线的γ δ T细胞在其免疫应答中表现出先天和适应性特征，并具有针对各种病毒的有效抗病毒活性。然而，γ δ T细胞在HPAI H5 N1病毒感染中的作用仍不清楚。在这项研究中，我们发现γ δ T细胞在防御HPAI H5 N1病毒感染中提供了至关重要的保护功能。HPAI H5 N1病毒可以直接激活γ δ T细胞，导致增强的CD 69表达和IFN-γ分泌。重要的是，我们发现HPAI H5 N1病毒血凝素（HA）蛋白的三聚体而不是单体可以直接激活γ δ T细胞。HA诱导的γ δ T细胞活化依赖于唾液酸受体和HA糖基化，这种活化可以被磷酸酶钙调磷酸酶抑制剂环孢菌素A抑制，但不能被磷脂酰肌醇3-激酶（PI 3-K）抑制剂渥曼青霉素和LY 294002抑制。我们的研究结果提供了进一步了解γ δ T细胞介导的先天性和过继性免疫反应对HPAI H5 N1病毒感染的机制，这有助于开发新的治疗策略，为H5 N1感染的治疗在未来。
Given the high mortality rate (>50%) and potential danger of intrapersonal transmission, highly pathogenic avian influenza (HPAI) H5N1 epidemics still pose a significant threat to humans. gamma delta T cells, which participate on the front line of the host immune defense, demonstrate both innate, and adaptive characteristics in their immune response and have potent antiviral activity against various viruses. However, the roles of gamma delta T cells in HPAI H5N1 viral infection remain unclear. In this study, we found that gamma delta T cells provided a crucial protective function in the defense against HPAI H5N1 viral infection. HPAI H5N1 viruses could directly activate gamma delta T cells, leading to enhanced CD69 expression and IFN-gamma secretion. Importantly, we found that the trimer but not the monomer of HPAI H5N1 virus hemagglutinin (HA) proteins could directly activate gamma delta T cells. HA-induced gamma delta T cell activation was dependent on both sialic acid receptors and HA glycosylation, and this activation could be inhibited by the phosphatase calcineurin inhibitor cyclosporin A but not by the phosphatidylinositol 3-kinase (PI3-K) inhibitors wortmannin and LY294002. Our findings provide a further understanding the mechanism underlying gamma delta T cell-mediated innate and adoptive immune responses against HPAI H5N1 viral infection, which helps to develop novel therapeutic strategies for the treatment of H5N1 infection in the future.