Bekale Raymonde B, Maphasa Retsepile E, D'Souza Sarah, Hsu Nai Jen, Walters Avril, Okugbeni Naomi, Kinnear Craig, Jacobs Muazzam, Sampson Samantha L, Meyer Mervin, Morse Gene D, Dube Admire
Infectious Disease Nanomedicine Research Group, School of Pharmacy, University of the Western Cape, Cape Town 7535, South Africa.
Division of Immunology, Department of Pathology, University of Cape Town, Cape Town 7701, South Africa.
ACS Infect Dis. 2025 Mar 14;11(3):610-625. doi: 10.1021/acsinfecdis.4c00713. Epub 2025 Feb 25.
Tuberculosis (TB) is the leading cause of death from infectious disease. Macrophages are the primary immune responders and become the primary host cells for the causative agent . Following the uptake of , the inherent antimicrobial action of macrophages is dampened, enabling the bacterium to reside within these cells and multiply. Rising resistance of to antibiotics has led to the investigation of novel approaches for the treatment of TB. Here, we report a host-directed approach, employing biomimetic Curdlan poly(lactic--glycolic acid) (C-PLGA) nanoparticles (NPs), and examine autophagy induction in infected macrophages, eradication of and immune modulation in a mouse model. We demonstrate that the NPs induce autophagy in -infected macrophages. Treatment of H37Rv infected C57BL/6 mice with these NPs reduced burden in the lungs of mice and modulated cytokines and chemokines and this work demonstrates that these immunomodulatory NPs are a potential treatment approach for TB.
结核病（TB）是传染病致死的主要原因。巨噬细胞是主要的免疫应答细胞，也是病原体的主要宿主细胞。在摄取（此处原文似乎缺失部分内容）后，巨噬细胞固有的抗菌作用受到抑制，使细菌能够在这些细胞内生存并繁殖。结核杆菌对抗生素的耐药性不断增强，促使人们研究治疗结核病的新方法。在此，我们报告一种宿主导向方法，即使用仿生的可德兰聚（乳酸-乙醇酸）（C-PLGA）纳米颗粒（NPs），并在感染的巨噬细胞中检测自噬诱导、结核杆菌的清除以及在小鼠模型中的免疫调节作用。我们证明这些纳米颗粒可在结核杆菌感染的巨噬细胞中诱导自噬。用这些纳米颗粒治疗H37Rv感染的C57BL/6小鼠可减轻小鼠肺部的结核杆菌负担，并调节细胞因子和趋化因子，这项研究表明这些免疫调节纳米颗粒是治疗结核病的一种潜在方法。
