Crilly Nathan P, Ayeh Samuel K, Karakousis Petros C
Department of Molecular and Comparative Pathobiology, Johns Hopkins School of Medicine, Baltimore, MD, United States.
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Front Immunol. 2021 Jan 22;11:623119. doi: 10.3389/fimmu.2020.623119. eCollection 2020.
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.
鸟分枝杆菌复合体(MAC)是导致发病和死亡的一个日益重要的原因,它可引起肺部疾病患者的肺部感染以及艾滋病患者的播散性疾病。MAC已演化出多种毒力策略来颠覆免疫反应并在受感染宿主中持续存在。目前针对MAC的治疗具有挑战性,需要联合使用多种抗生素并长期给药(痰培养转阴后至少12个月)。此外,即使感染被根除,许多患者仍会遗留残余肺功能障碍。为应对结核病患者管理中面临的类似挑战,最近的注意力集中在开发新型辅助性宿主导向疗法(HDTs)上,目标是通过免疫防御加速分枝杆菌的清除,并减少或逆转分枝杆菌引起的肺损伤。在本综述中,我们将总结支持针对MAC的特定辅助性HDTs的证据,重点是重新利用针对各种不同细胞途径的现有免疫调节药物。我们还强调了值得进一步研究的领域。