Type IIFN modulates innate and specific antiviral immunity
Type IIFN modulates innate and specific antiviral immunity
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DOI：
10.4049/jimmunol.164.8.4220
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发表时间：
2000-04-15
影响因子：
4.4
通讯作者：
Levy, DE
中科院分区：
文献类型：
--
作者：
Durbin, JE;Fernandez-Sesma, A;Levy, DE
IFN通过诱导抗病毒状态和调节免疫应答来保护免受病毒感染。使用在IFN信号传导的多个方面有缺陷的小鼠，我们发现I型和II型IFN在流感病毒疾病的解决中发挥不同但互补的作用。这两种类型的干扰素的影响，由T淋巴细胞产生的细胞因子的配置文件，与一个显着的偏差向Th 2分化的情况下发生的反应，任何HN，然而，虽然Th 1的偏差产生通过抑制Th 2分化IFN-γ是不需要解决感染，I型IFN反应性的损失导致恶化的疾病病理特征为粒细胞性肺炎性浸润。对I型IFN的反应性不影响病毒特异性细胞毒性淋巴细胞的产生或病毒清除率，但通过I型IFN依赖性途径诱导感染肺中的IL-10和IL-15与对病毒的保护性反应相关。两种IFN途径的联合丧失导致严重极化的促炎免疫应答和疾病恶化。这些结果揭示了I型IFN在协调宿主对病毒感染的应答和在不直接影响病毒复制的情况下控制炎症中的意想不到的作用。免疫学杂志，2000，164：4220-4228.
IFNs protect from virus infection by inducing an antiviral state and by modulating the immune response. Using mice deficient in multiple aspects of IFN signaling, we found that type I and type II IFN play distinct although complementing roles in the resolution of influenza viral disease. Both types of IFN influenced the profile of cytokines produced by T lymphocytes, with a significant bias toward Th2 differentiation occurring in the absence of responsiveness to either HN, However, although a Th1 bias produced through inhibition of Th2 differentiation by IFN-gamma was not required to resolve infection, loss of type I IFN responsiveness led to exacerbated disease pathology characterized by granulocytic pulmonary inflammatory infiltrates. Responsiveness to type I IFN did not influence the generation;of virus-specific cytotoxic lymphocytes or the rate of viral clearance, but induction of IL-10 and IL-15 in infected lungs through a type I IFN-dependent pathway correlated with a protective response to virus. Combined loss of both IFN pathways led to a severely polarized proinflammatory immune response and exacerbated disease, These results reveal an unexpected role for type I IFN in coordinating the host response to viral infection and controlling inflammation in the absence of a direct effect on virus replication. The Journal of Immunology, 2000, 164: 4220-4228.