Department of Biological Sciences, New York City College of Technology, Brooklyn, NY, USA.
Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
J Pathol. 2020 Apr;250(5):636-646. doi: 10.1002/path.5407. Epub 2020 Mar 24.
Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), has co-evolved with the human immune system and utilizes multiple strategies to persist within infected cells, to hijack several immune mechanisms, and to cause severe pathology and tissue damage in the host. This delays the efficacy of current antibiotic therapy and contributes to the evolution of multi-drug-resistant strains. These challenges led to the development of the novel approach in TB treatment that involves therapeutic targeting of host immune response to control disease pathogenesis and pathogen growth, namely, host-directed therapies (HDTs). Such HDT approaches can (1) enhance the effect of antibiotics, (2) shorten treatment duration for any clinical form of TB, (3) promote development of immunological memory that could protect against relapse, and (4) ameliorate the immunopathology including matrix destruction and fibrosis associated with TB. In this review we discuss TB-HDT candidates shown to be of clinical relevance that thus could be developed to reduce pathology, tissue damage, and subsequent impairment of pulmonary function. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
结核分枝杆菌是结核病（TB）的病原体，它与人体免疫系统共同进化，利用多种策略在感染细胞内持续存在，劫持多种免疫机制，并在宿主中引起严重的病理和组织损伤。这延迟了当前抗生素治疗的效果，并导致了多药耐药株的进化。这些挑战导致了结核病治疗的新方法的发展，即通过治疗性靶向宿主免疫反应来控制疾病发病机制和病原体生长，即宿主定向治疗（HDT）。这种 HDT 方法可以（1）增强抗生素的效果，（2）缩短任何临床形式的结核病的治疗时间，（3）促进免疫记忆的发展，从而可以预防复发，（4）改善与结核病相关的免疫病理学，包括基质破坏和纤维化。在这篇综述中，我们讨论了显示出临床相关性的 TB-HDT 候选物，这些候选物可以开发出来减轻病理学、组织损伤和随后的肺功能障碍。
