Leiden University, Leiden, The Netherlands.
Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
Trends Pharmacol Sci. 2022 Apr;43(4):293-304. doi: 10.1016/j.tips.2021.11.016. Epub 2021 Dec 13.
Host-directed therapies (HDTs) that modulate host-pathogen interactions offer an innovative strategy to combat Mycobacterium tuberculosis (Mtb) infections. When combined with tuberculosis (TB) antibiotics, HDTs could contribute to improving treatment outcomes, reducing treatment duration, and preventing resistance development. Translation of the interplay of host-pathogen interactions leveraged by HDTs towards therapeutic outcomes in patients is challenging. Quantitative understanding of the multifaceted nature of the host-pathogen interactions is vital to rationally design HDT strategies. Here, we (i) provide an overview of key Mtb host-pathogen interactions as basis for HDT strategies; and (ii) discuss the components and utility of quantitative systems pharmacology (QSP) models to inform HDT strategies. QSP models can be used to identify and optimize treatment targets, to facilitate preclinical to human translation, and to design combination treatment strategies.
宿主导向治疗（HDTs）通过调节宿主-病原体相互作用，为抗击结核分枝杆菌（Mtb）感染提供了一种创新策略。当与结核病（TB）抗生素联合使用时，HDTs 可能有助于改善治疗效果、缩短治疗时间并预防耐药性的产生。将宿主-病原体相互作用的相互作用转化为患者治疗效果具有挑战性。定量理解宿主-病原体相互作用的多方面性质对于合理设计 HDT 策略至关重要。在这里，我们：（i）提供 Mtb 宿主-病原体相互作用的概述，作为 HDT 策略的基础；（ii）讨论定量系统药理学（QSP）模型的组成部分和用途，以提供 HDT 策略信息。QSP 模型可用于确定和优化治疗靶点，促进从临床前到人体的转化，并设计联合治疗策略。
