Targeting Macrophage Dysregulation for Viral Infections: Novel Targets for Immunomodulators.
Targeting Macrophage Dysregulation for Viral Infections: Novel Targets for Immunomodulators.
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DOI：
10.3389/fimmu.2021.768695
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发表时间：
2021
影响因子：
7.3
通讯作者：
Gavegnano C
中科院分区：
文献类型：
--
作者：
Reece MD;Taylor RR;Song C;Gavegnano C
人类免疫缺陷病毒（HIV-1）治愈的主要障碍是潜伏的病毒储库，尽管抗逆转录病毒治疗（ART），其仍然存在，包括在组织和中枢神经系统（CNS）的避难所部位全身发现的非分裂骨髓储库。与活化的CD 4 + T细胞在初始感染期间经历快速细胞死亡（由于快速病毒复制动力学）不同，病毒复制动力学在非分裂骨髓细胞中延迟，导致感染的巨噬细胞和巨噬细胞样细胞的长期存活。同时，巨噬细胞中的持续性炎症导致免疫失调，这是HIV-1（PLWH）感染者中包括心血管疾病（CVD）和神经功能缺损在内的共病的关键驱动因素。巨噬细胞活化和失调也是其他病毒感染（包括SARS-CoV-2、流感和基孔肯雅病毒）疾病进展的关键驱动因素，强调了巨噬细胞与病毒感染背景下疾病进展、发病机制和合并症之间的相互作用。本文综述了巨噬细胞在HIV-1和相关共病、SARS-CoV-2和其他病毒的持续存在和发病机制中的作用。一个特别的重点是给予新的免疫调节目标的关键事件驱动骨髓细胞失调和水库的维护，在各种各样的病毒感染。
A major barrier to human immunodeficiency virus (HIV-1) cure is the latent viral reservoir, which persists despite antiretroviral therapy (ART), including across the non-dividing myeloid reservoir which is found systemically in sanctuary sites across tissues and the central nervous system (CNS). Unlike activated CD4+ T cells that undergo rapid cell death during initial infection (due to rapid viral replication kinetics), viral replication kinetics are delayed in non-dividing myeloid cells, resulting in long-lived survival of infected macrophages and macrophage-like cells. Simultaneously, persistent inflammation in macrophages confers immune dysregulation that is a key driver of co-morbidities including cardiovascular disease (CVD) and neurological deficits in people living with HIV-1 (PLWH). Macrophage activation and dysregulation is also a key driver of disease progression across other viral infections including SARS-CoV-2, influenza, and chikungunya viruses, underscoring the interplay between macrophages and disease progression, pathogenesis, and comorbidity in the viral infection setting. This review discusses the role of macrophages in persistence and pathogenesis of HIV-1 and related comorbidities, SARS-CoV-2 and other viruses. A special focus is given to novel immunomodulatory targets for key events driving myeloid cell dysregulation and reservoir maintenance across a diverse array of viral infections.