Department of Immunology, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany.
Institute of Immunology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Südufer 10, 17493 Greifswald - Insel Riems, Germany.
Nat Rev Drug Discov. 2018 Jan;17(1):35-56. doi: 10.1038/nrd.2017.162. Epub 2017 Sep 22.
Despite the recent increase in the development of antivirals and antibiotics, antimicrobial resistance and the lack of broad-spectrum virus-targeting drugs are still important issues and additional alternative approaches to treat infectious diseases are urgently needed. Host-directed therapy (HDT) is an emerging approach in the field of anti-infectives. The strategy behind HDT is to interfere with host cell factors that are required by a pathogen for replication or persistence, to enhance protective immune responses against a pathogen, to reduce exacerbated inflammation and to balance immune reactivity at sites of pathology. Although HDTs encompassing interferons are well established for the treatment of chronic viral hepatitis, novel strategies aimed at the functional cure of persistent viral infections and the development of broad-spectrum antivirals against emerging viruses seem to be crucial. In chronic bacterial infections, such as tuberculosis, HDT strategies aim to enhance the antimicrobial activities of phagocytes and to curtail inflammation through interference with soluble factors (such as eicosanoids and cytokines) or cellular factors (such as co-stimulatory molecules). This Review describes current progress in the development of HDTs for viral and bacterial infections, including sepsis, and the challenges in bringing these new approaches to the clinic.
尽管最近抗病毒药物和抗生素的发展有所增加，但抗菌药物耐药性和缺乏广谱病毒靶向药物仍然是重要问题，迫切需要额外的替代方法来治疗传染病。宿主导向治疗 (HDT) 是抗感染领域的一种新兴方法。HDT 的背后的策略是干扰病原体复制或持续所需的宿主细胞因子，增强针对病原体的保护性免疫反应，减少过度炎症，并平衡病理学部位的免疫反应性。虽然针对干扰素的 HDTs 已被广泛用于治疗慢性病毒性肝炎，但针对持续性病毒感染的功能治愈和开发针对新兴病毒的广谱抗病毒药物的新策略似乎至关重要。在慢性细菌感染（如结核病）中，HDT 策略旨在通过干扰可溶性因子（如类二十烷酸和细胞因子）或细胞因子（如共刺激分子）来增强吞噬细胞的抗菌活性并减少炎症。这篇综述描述了用于病毒和细菌感染（包括败血症）的 HDT 的最新进展，以及将这些新方法推向临床的挑战。
