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一场完美风暴:衰老、人类免疫缺陷病毒感染与炎性小体失调的交汇

A Perfect Storm: The Convergence of Aging, Human Immunodeficiency Virus Infection, and Inflammasome Dysregulation.

作者信息

Thirugnanam Siva, Rout Namita

机构信息

Division of Microbiology, Tulane National Primate Research Center, Covington, LA 70433, USA.

Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112, USA.

出版信息

Curr Issues Mol Biol. 2024 May 15;46(5):4768-4786. doi: 10.3390/cimb46050287.

Abstract

The emergence of combination antiretroviral therapy (cART) has greatly transformed the life expectancy of people living with HIV (PWH). Today, over 76% of the individuals with HIV have access to this life-saving therapy. However, this progress has come with a new challenge: an increase in age-related non-AIDS conditions among patients with HIV. These conditions manifest earlier in PWH than in uninfected individuals, accelerating the aging process. Like PWH, the uninfected aging population experiences immunosenescence marked by an increased proinflammatory environment. This phenomenon is linked to chronic inflammation, driven in part by cellular structures called inflammasomes. Inflammatory signaling pathways activated by HIV-1 infection play a key role in inflammasome formation, suggesting a crucial link between HIV and a chronic inflammatory state. This review outlines the inflammatory processes triggered by HIV-1 infection and aging, with a focus on the inflammasomes. This review also explores current research regarding inflammasomes and potential strategies for targeting inflammasomes to mitigate inflammation. Further research on inflammasome signaling presents a unique opportunity to develop targeted interventions and innovative therapeutic modalities for combating HIV and aging-associated inflammatory processes.

摘要

联合抗逆转录病毒疗法(cART)的出现极大地改变了艾滋病毒感染者(PWH)的预期寿命。如今,超过76%的艾滋病毒感染者能够获得这种挽救生命的疗法。然而,这一进展带来了新的挑战:艾滋病毒感染者中与年龄相关的非艾滋病相关疾病有所增加。这些疾病在艾滋病毒感染者中比未感染个体更早出现,加速了衰老过程。与艾滋病毒感染者一样,未感染的老年人群也经历以促炎环境增加为特征的免疫衰老。这种现象与慢性炎症有关,部分由称为炎性小体的细胞结构驱动。由HIV-1感染激活的炎症信号通路在炎性小体形成中起关键作用,这表明艾滋病毒与慢性炎症状态之间存在重要联系。本综述概述了由HIV-1感染和衰老引发的炎症过程,重点关注炎性小体。本综述还探讨了目前关于炎性小体的研究以及针对炎性小体减轻炎症的潜在策略。对炎性小体信号传导的进一步研究为开发针对性干预措施和创新治疗方法以对抗艾滋病毒和与衰老相关的炎症过程提供了独特的机会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bd0/11119826/97fbeaeceb2f/cimb-46-00287-g001.jpg

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