Kalra Rashi, Tiwari Drishti, Dkhar Hedwin Kitdorlang, Bhagyaraj Ella, Kumar Rakesh, Bhardwaj Anshu, Gupta Pawan
Department of Molecular Biology, CSIR-Institute of Microbial Technology, Chandigarh-160036, India.
Bioinformatics Center, CSIR-Institute of Microbial Technology, Chandigarh-160036, India.
Int Rev Immunol. 2023;42(1):43-70. doi: 10.1080/08830185.2021.1990277. Epub 2021 Oct 22.
Despite new approaches in the diagnosis and treatment of tuberculosis (TB), it continues to be a major health burden. Several immunotherapies that potentiate the immune response have come up as adjuncts to drug therapies against drug resistant TB strains; however, there needs to be an urgent appraisal of host specific drug targets for improving their clinical management and to curtail disease progression. Presently, various host directed therapies (HDTs) exist (repurposed drugs, nutraceuticals, monoclonal antibodies and immunomodulatory agents), but these mostly address molecules that combat disease progression.
The current review discusses major () survival paradigms inside the host and presents a plethora of host targets subverted by which can be further explored for future HDTs. The host factors unique to infection (in humans) have also been identified through an interaction mapping.
HDTs could become the next-generation adjunct therapies in order to counter antimicrobial resistance and virulence, as well as to reduce the duration of existing TB treatments. However, current scientific efforts are largely directed toward combatants rather than host molecules co-opted by for its survival. This might drive the immune system to a hyper-inflammatory condition; therefore, we emphasize that host factors subverted by , and their subsequent neutralization, must be considered for development of better HDTs.
尽管结核病的诊断和治疗有了新方法,但它仍然是一个主要的健康负担。几种增强免疫反应的免疫疗法已作为针对耐药结核菌株的药物疗法的辅助手段出现;然而,迫切需要对宿主特异性药物靶点进行评估,以改善其临床管理并遏制疾病进展。目前,存在各种宿主导向疗法(HDTs)(重新利用的药物、营养保健品、单克隆抗体和免疫调节剂),但这些大多针对对抗疾病进展的分子。
当前的综述讨论了宿主内主要的()生存模式,并提出了大量被()颠覆的宿主靶点,这些靶点可在未来的宿主导向疗法中进一步探索。通过()相互作用图谱也确定了(人类)感染所特有的宿主因素。
宿主导向疗法可能成为下一代辅助疗法,以对抗抗菌素耐药性和毒力,并缩短现有结核病治疗的疗程。然而,目前的科学努力主要针对战斗分子,而不是被()用于生存的宿主分子。这可能会使免疫系统陷入过度炎症状态;因此,我们强调,为了开发更好的宿主导向疗法,必须考虑被()颠覆的宿主因素及其随后的中和作用。