The New Frontier of Host-Directed Therapies for Mycobacterium avium Complex.
The New Frontier of Host-Directed Therapies for Mycobacterium avium Complex.
复制标题
宿主定向疗法的新领域，用于分枝杆菌复合体。
DOI：
10.3389/fimmu.2020.623119
复制
发表时间：
2020
影响因子：
7.3
通讯作者：
Karakousis PC
中科院分区：
文献类型：
--
作者：
Crilly NP;Ayeh SK;Karakousis PC
鸟分枝杆菌复合体（MAC）是一个越来越重要的发病率和死亡率的原因，并负责肺部感染的患者与潜在的肺部疾病和播散性疾病的艾滋病患者。MAC已经进化出各种毒力策略来破坏免疫反应并在受感染的宿主中持续存在。目前MAC的治疗是具有挑战性的，需要在很长一段时间内给予多种抗生素的组合（痰培养阴性后至少12个月）。此外，即使在根除感染后，许多患者仍有残余肺功能障碍。为了解决结核病患者管理面临的类似挑战，最近的注意力集中在开发新的抗结核、宿主导向疗法（HDTs）上，目的是通过免疫防御加速分枝杆菌的清除，减少或逆转分枝杆菌诱导的肺损伤。在这篇综述中，我们将总结支持MAC的特异性免疫抑制剂HDTs的证据，重点是针对各种不同细胞通路的现有免疫调节剂的再利用。我们还强调了值得进一步调查的领域。
Mycobacterium avium complex (MAC) is an increasingly important cause of morbidity and mortality, and is responsible for pulmonary infection in patients with underlying lung disease and disseminated disease in patients with AIDS. MAC has evolved various virulence strategies to subvert immune responses and persist in the infected host. Current treatment for MAC is challenging, requiring a combination of multiple antibiotics given over a long time period (for at least 12 months after negative sputum culture conversion). Moreover, even after eradication of infection, many patients are left with residual lung dysfunction. In order to address similar challenges facing the management of patients with tuberculosis, recent attention has focused on the development of novel adjunctive, host-directed therapies (HDTs), with the goal of accelerating the clearance of mycobacteria by immune defenses and reducing or reversing mycobacterial-induced lung damage. In this review, we will summarize the evidence supporting specific adjunctive, HDTs for MAC, with a focus on the repurposing of existing immune-modulatory agents targeting a variety of different cellular pathways. We also highlight areas meriting further investigation.