Kak Gunjan, Raza Mohsin, Tiwari Brijendra K
From the Infectious Disease Immunology Lab, Dr. B R Ambedkar Center for Biomedical Research, University of Delhi, Delhi, 110007, India.
Department of Biochemistry, University of Delhi, South Campus, New Delhi, 110021, India.
Biomol Concepts. 2018 May 30;9(1):64-79. doi: 10.1515/bmc-2018-0007.
A key player in driving cellular immunity, IFN-γ 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 anti-microbial functions and affecting cellular proliferation and apoptosis. A complex interplay between immune cell activity and IFN-γ through coordinated integration of signals from other pathways involving cytokines and Pattern Recognition Receptors (PRRs) such as Interleukin (IL)-4, TNF-α, 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-γ. Consequently, IFN-γ stimulated cells display altered expression of many such target genes which mediate its downstream effector functions. The importance of IFN-γ is further reinforced by the fact that mice possessing disruptions in the IFN-γ 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-γ endowed immune-protection. Thus, IFN-γ 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.
作为驱动细胞免疫的关键因子，γ干扰素（IFN-γ）能够协调多种保护性功能，以增强对感染和癌症的免疫反应。它可通过增强抗原加工与呈递、增加白细胞迁移、诱导抗病毒状态、增强抗菌功能以及影响细胞增殖和凋亡来发挥免疫调节作用。免疫细胞活性与IFN-γ之间通过来自其他途径（涉及细胞因子和模式识别受体（PRR），如白细胞介素（IL）-4、肿瘤坏死因子-α、脂多糖（LPS）、I型干扰素（IFN）等）信号的协同整合产生复杂的相互作用，从而引发一系列促炎反应。微阵列数据揭示了众多转录调控受IFN-γ影响的基因。因此，IFN-γ刺激的细胞表现出许多此类靶基因表达的改变，这些基因介导其下游效应功能。IFN-γ基因或其受体存在缺陷的小鼠对传染病极度易感并迅速死亡，这一事实进一步凸显了IFN-γ的重要性。在本综述中，我们试图阐明这种多功能细胞因子的生物学功能和生理重要性。还讨论了其生物活性在几种传染病和自身免疫性疾病中的功能意义。作为一种应对策略，许多致病物种已设计出方法来对抗IFN-γ赋予的免疫保护。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至关重要，这些方面对于消除各种感染和自身免疫性疾病也具有巨大的治疗意义。
