Hromić-Jahjefendić Altijana, Aljabali Alaa A A
Department of Genetics and Bioengineering, Faculty of Engineering and Natural Sciences, International University of Sarajevo, Sarajevo, Bosnia and Herzegovina.
Faculty of Pharmacy, Department of Pharmaceutics and Pharmaceutical Technology, Yarmouk University, Irbid, Jordan.
Prog Mol Biol Transl Sci. 2025;213:31-71. doi: 10.1016/bs.pmbts.2024.10.004. Epub 2025 Jan 26.
The COVID-19 pandemic, instigated by the novel coronavirus SARS-CoV-2, has emerged as a significant global health challenge, demanding a profound grasp of the immune response. The innate immune system, a multifaceted network encompassing pattern recognition receptors (PRRs) and effector cells, assumes a pivotal function in detecting and countering this viral assailant. Toll-like receptors (TLRs), situated on immune cell surfaces and within endosomes, play a central role in recognizing SARS-CoV-2. TLR-2 and TLR-4 discern specific viral constituents, such as the spike (S) protein, setting off inflammatory signaling cascades and catalyzing the generation of type I interferons. Intracellular PRRs, including the RIG-I-like receptors (RLRs), RIG-I and MDA5, detect viral RNA within the cytoplasm of infected cells, provoking antiviral responses by initiating the synthesis of type I interferons. The equilibrium between interferons and pro-inflammatory cytokines dictates the outcomes of the disease. Interferons play an indispensable role in governing viral replication, while unregulated cytokine production can result in tissue harm and inflammation. This intricate dynamic underpins therapeutic strategies aimed at regulating immune responses in individuals grappling with COVID-19. Natural killer (NK) cells, with their capacity to recognize infected cells through the "missing self" phenomenon and activating receptors, make significant contributions to the defense against SARS-CoV-2. NK cells play a pivotal role in eliminating infected cells and boosting immune responses through antibody-dependent cell-mediated cytotoxicity (ADCC). In conclusion, comprehending the interplay among PRRs, interferons, and NK cells within innate immunity is paramount for discerning and combatting SARS-CoV-2. This comprehension illuminates therapeutic interventions and vaccine development, casting light on our endeavors to confront this worldwide health crisis.
由新型冠状病毒SARS-CoV-2引发的新冠疫情已成为一项重大的全球健康挑战，需要深刻理解免疫反应。固有免疫系统是一个包含模式识别受体（PRR）和效应细胞的多方面网络，在检测和对抗这种病毒攻击者方面发挥着关键作用。位于免疫细胞表面和内体中的Toll样受体（TLR）在识别SARS-CoV-2中起核心作用。TLR-2和TLR-4识别特定的病毒成分，如刺突（S）蛋白，引发炎症信号级联反应并催化I型干扰素的产生。细胞内PRR，包括视黄酸诱导基因I样受体（RLR）、视黄酸诱导基因I（RIG-I）和黑色素瘤分化相关基因5（MDA5），在受感染细胞的细胞质中检测病毒RNA，通过启动I型干扰素的合成引发抗病毒反应。干扰素和促炎细胞因子之间的平衡决定了疾病的结果。干扰素在控制病毒复制中发挥着不可或缺的作用，而不受调节的细胞因子产生会导致组织损伤和炎症。这种复杂的动态机制是旨在调节新冠患者免疫反应的治疗策略的基础。自然杀伤（NK）细胞能够通过“缺失自我”现象和激活受体识别受感染细胞，为抵御SARS-CoV-2做出了重大贡献。NK细胞在通过抗体依赖性细胞介导的细胞毒性（ADCC）消除受感染细胞和增强免疫反应方面发挥着关键作用。总之，了解固有免疫中PRR、干扰素和NK细胞之间的相互作用对于识别和对抗SARS-CoV-2至关重要。这种理解为治疗干预和疫苗开发提供了启示，照亮了我们应对这一全球健康危机的努力。
