Type-I Interferon Responses: From Friend to Foe in the Battle against Chronic Viral Infection.
Type-I Interferon Responses: From Friend to Foe in the Battle against Chronic Viral Infection.
复制标题
DOI：
10.3389/fimmu.2016.00609
复制
发表时间：
2016
影响因子：
7.3
通讯作者：
Lamarre A
中科院分区：
文献类型：
--
作者：
Murira A;Lamarre A
I型干扰素（IFN-I）长期以来一直被认为是有效抗病毒反应的关键贡献者。在急性病毒感染的背景下，这种多效性细胞因子的作用被更广泛地理解为触发细胞中的抗病毒状态并增强适应性免疫反应。在诱导先天免疫应答后，IFN-1触发干扰素刺激基因（ISG）的表达，其上调免疫细胞的效应子功能（例如，树突状细胞、B细胞和T细胞），以成功解决感染。然而，新出现的证据表明，在慢性感染过程中的病毒持续存在可能是由持续IFN-1表达后的有害免疫调节作用驱动的。在这种情况下，IFN-I和ISG的升高与病毒持续存在和病毒载量升高直接相关。值得注意的是，IFN-1表达、ISG和病毒持续存在之间的相关性可能是慢性感染的原因或结果，这是建立IFN-1应答的二分性的重要区别。这篇小型综述的目的是（i）总结IFN-1和下游效应器反应之间的相互作用，因此（ii）描述这种细胞因子在慢性感染中对正性和负性免疫调节的功能。这是一个重要的考虑因素，考虑到目前IFN-1在慢性病毒感染中的治疗性给药，尽管出现了越来越有效的抗病毒方案，但预计其治疗意义将继续存在。此外，阐明病毒之间的相互作用和干扰素-I的背景下的抗病毒反应将阐明途径更有效的治疗和预防措施，对慢性病毒感染。
Type I interferons (IFN-I) have long been heralded as key contributors to effective antiviral responses. More widely understood in the context of acute viral infection, the role of this pleiotropic cytokine has been characterized as triggering antiviral states in cells and potentiating adaptive immune responses. Upon induction in the innate immune response, IFN-I triggers the expression of interferon-stimulated genes (ISGs), which upregulate the effector function of immune cells (e.g., dendritic cells, B cells, and T cells) toward successful resolution of infections. However, emerging lines of evidence reveal that viral persistence in the course of chronic infections could be driven by deleterious immunomodulatory effects upon sustained IFN-I expression. In this setting, elevation of IFN-I and ISGs is directly correlated to viral persistence and elevated viral loads. It is important to note that the correlation among IFN-I expression, ISGs, and viral persistence may be a cause or effect of chronic infection and this is an important distinction to make toward establishing the dichotomous nature of IFN-I responses. The aim of this mini review is to (i) summarize the interaction between IFN-I and downstream effector responses and therefore (ii) delineate the function of this cytokine on positive and negative immunoregulation in chronic infection. This is a significant consideration given the current therapeutic administration of IFN-I in chronic viral infections whose therapeutic significance is projected to continue despite emergence of increasingly efficacious antiviral regimens. Furthermore, elucidation of the interplay between virus and the antiviral response in the context of IFN-I will elucidate avenues toward more effective therapeutic and prophylactic measures against chronic viral infections.
登录
查看更多内容
干扰素-α：系统性红斑狼疮的治疗靶点。
影响因子：
2.3
作者：
Crow, Mary K.
通讯作者：
Crow, Mary K.
影响因子：
4.4
作者：
CHEN, JZ;TROUNSTINE, M;HUSZAR, D
通讯作者：
HUSZAR, D
DOI：
10.1084/jem.20101773
发表时间：
2011-05-09
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Fahey LM;Wilson EB;Elsaesser H;Fistonich CD;McGavern DB;Brooks DG
通讯作者：
Brooks DG
影响因子：
4.4
作者：
Fuller, MJ;Zajac, AJ
通讯作者：
Zajac, AJ
影响因子：
3.7
作者：
Cagigi, Alberto;Du, Likun;Nilsson, Anna
通讯作者：
Nilsson, Anna