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巨噬细胞对用于结核病治疗的自噬诱导纳米药物的反应及机遇

The Macrophage Response to and Opportunities for Autophagy Inducing Nanomedicines for Tuberculosis Therapy.

作者信息

Maphasa Retsepile E, Meyer Mervin, Dube Admire

机构信息

Infectious Disease Nanomedicine Research Group, School of Pharmacy, University of the Western Cape, Cape Town, South Africa.

DST/Mintek Nanotechnology Innovation Centre, Biolabels Node, Department of Biotechnology, University of the Western Cape, Cape Town, South Africa.

出版信息

Front Cell Infect Microbiol. 2021 Feb 8;10:618414. doi: 10.3389/fcimb.2020.618414. eCollection 2020.

Abstract

The major causative agent of tuberculosis (TB), i.e., , has developed mechanisms to evade host defense responses and persist within host cells for prolonged periods of time. is also increasingly resistant to existing anti-TB drugs. There is therefore an urgent need to develop new therapeutics for TB and host directed therapies (HDTs) hold potential as effective therapeutics for TB. There is growing interest in the induction of autophagy in host cells using autophagy inducing compounds (AICs). Nanoparticles (NPs) can enhance the effect of AICs, thus improving stability, enabling cell targeting and providing opportunities for multimodal therapy. In this review, we focus on the macrophage responses to infection, in particular, the mechanistic aspects of autophagy and the evasion of autophagy by intracellular . Due to the overlap between the onset of autophagy and apoptosis; we also focus on the relationship between apoptosis and autophagy. We will also review known AICs in the context of infection. Finally, we discuss the applications of NPs in inducing autophagy with the intention of sharing insights to encourage further research and development of nanomedicine HDTs for TB therapy.

摘要

结核病(TB)的主要病原体,即结核分枝杆菌,已经形成了逃避宿主防御反应并在宿主细胞内长期存活的机制。结核分枝杆菌对现有的抗结核药物也越来越耐药。因此,迫切需要开发新的结核病治疗方法,而宿主导向疗法(HDTs)有望成为有效的结核病治疗方法。使用自噬诱导化合物(AICs)诱导宿主细胞自噬的研究兴趣日益浓厚。纳米颗粒(NPs)可以增强AICs的效果,从而提高稳定性、实现细胞靶向并为多模式治疗提供机会。在本综述中,我们重点关注巨噬细胞对结核分枝杆菌感染的反应,特别是自噬的机制方面以及细胞内结核分枝杆菌对自噬的逃避。由于自噬和凋亡的起始存在重叠,我们还重点关注凋亡与自噬之间的关系。我们还将在结核分枝杆菌感染的背景下综述已知的AICs。最后,我们讨论NPs在诱导自噬中的应用,旨在分享见解,以鼓励进一步开展纳米医学HDTs用于结核病治疗的研究和开发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52d9/7897680/866d024466e1/fcimb-10-618414-g001.jpg

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