Interferon-gamma (IFN-γ): Exploring its implications in infectious diseases
Interferon-gamma (IFN-γ): Exploring its implications in infectious diseases
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DOI：
10.1515/bmc-2018-0007
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发表时间：
2018-01-01
影响因子：
--
通讯作者：
Tiwari, Brijendra K.
中科院分区：
文献类型：
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作者：
Kak, Gunjan;Raza, Mohsin;Tiwari, Brijendra K.
作为驱动细胞免疫的关键参与者，IFN-γ能够协调许多保护功能，以增强感染和癌症的免疫反应。它可以通过增强抗原加工和呈递、增加白细胞运输、诱导抗病毒状态、增强抗微生物功能以及影响细胞增殖和凋亡来表现其免疫调节作用。免疫细胞活性和IFN-γ之间的复杂相互作用通过来自涉及细胞因子和模式识别受体（PRR）如白细胞介素（IL）-4，TNF-α，脂多糖（LPS），I型干扰素（IFN）等的其他途径的信号的协调整合导致促炎反应级联的启动。微阵列数据已经揭示了许多基因的转录调控受到IFN-γ的影响。因此，IFN-γ刺激的细胞显示出许多介导其下游效应子功能的靶基因的表达改变。IFN-γ的重要性进一步得到了以下事实的加强：IFN-γ基因或其受体被破坏的小鼠对传染病具有极端的易感性，并迅速死于传染病。在这篇综述中，我们试图阐明这种多功能细胞因子的生物学功能和生理学意义。它的生物活性在几种感染性疾病和自身免疫性病理功能的影响也进行了讨论。作为一种对抗策略，许多致命的病原性物种已经设计出阻止IFN-γ赋予的免疫保护的方法。因此，IFN-γ介导的宿主-病原体相互作用对于我们理解疾病机制是至关重要的，并且这些方面也表现出对于消除各种感染和自身免疫性病症的巨大治疗重要性。
A key player in driving cellular immunity, IFN-gamma is capable of orchestrating numerous protective functions to heighten immune responses in infections and cancers. It can exhibit its immunomodulatory effects by enhancing antigen processing and presentation, increasing leukocyte trafficking, inducing an anti-viral state, boosting the antimicrobial functions and affecting cellular proliferation and apoptosis. A complex interplay between immune cell activity and IFN-gamma through coordinated integration of signals from other pathways involving cytokines and Pattern Recognition Receptors (PRRs) such as Interleukin (IL)-4, TNF-alpha, Lipopolysaccharide (LPS), Type-I Interferons (IFNs) etc. leads to initiation of a cascade of pro-inflammatory responses. Microarray data has unraveled numerous genes whose transcriptional regulation is influenced by IFN-gamma. Consequently, IFN-gamma stimulated cells display altered expression of many such target genes which mediate its downstream effector functions. The importance of IFN-gamma is further reinforced by the fact that mice possessing disruptions in the IFN-gamma gene or its receptor develop extreme susceptibility to infectious diseases and rapidly succumb to them. In this review, we attempt to elucidate the biological functions and physiological importance of this versatile cytokine. The functional implications of its biological activity in several infectious diseases and autoimmune pathologies are also discussed. As a counter strategy, many virulent pathogenic species have devised ways to thwart IFN-gamma endowed immune-protection. Thus, IFN-gamma mediated host-pathogen interactions are critical for our understanding of disease mechanisms and these aspects also manifest enormous therapeutic importance for the annulment of various infections and autoimmune conditions.