Mycobacterial Genetics Unit, Institut Pasteur, Paris, France.
Instituto de Nanociencia de Aragon, Universidad de Zaragoza and CIBER-BBN, Saragossa, Spain.
J Nanobiotechnology. 2019 Jan 25;17(1):15. doi: 10.1186/s12951-018-0439-x.
Infectious diseases are still a leading cause of death and, with the emergence of drug resistance, pose a great threat to human health. New drugs and strategies are thus urgently needed to improve treatment efficacy and limit drug-associated side effects. Nanotechnology-based drug delivery systems are promising approaches, offering hope in the fight against drug resistant bacteria. However, how nanocarriers influence the response of innate immune cells to bacterial infection is mostly unknown.
Here, we used Mycobacterium tuberculosis as a model of bacterial infection to examine the impact of mannose functionalization of chitosan nanocarriers (CS-NCs) on the human macrophage response. Both ungrafted and grafted CS-NCs were similarly internalized by macrophages, via an actin cytoskeleton-dependent process. Although tri-mannose ligands did not modify the capacity of CS-NCs to escape lysosomal degradation, they profoundly remodeled the response of M. tuberculosis-infected macrophages. mRNA sequencing showed nearly 900 genes to be differentially expressed due to tri-mannose grafting. Unexpectedly, the set of modulated genes was enriched for pathways involved in cell metabolism, particularly oxidative phosphorylation and sugar metabolism.
The ability to modulate cell metabolism by grafting ligands at the surface of nanoparticles may thus be a promising strategy to reprogram immune cells and improve the efficacy of encapsulated drugs.
传染病仍然是导致死亡的主要原因，而且随着耐药性的出现，对人类健康构成了巨大威胁。因此，迫切需要新的药物和策略来提高治疗效果并限制与药物相关的副作用。基于纳米技术的药物递送系统是很有前途的方法，为对抗耐药菌带来了希望。然而，纳米载体如何影响固有免疫细胞对细菌感染的反应在很大程度上尚不清楚。
在这里，我们使用结核分枝杆菌作为细菌感染的模型，研究了壳聚糖纳米载体（CS-NC）的甘露糖功能化对人巨噬细胞反应的影响。未接枝和接枝的 CS-NC 均通过肌动蛋白细胞骨架依赖性过程被巨噬细胞类似地内化。尽管三甘露糖配体并未改变 CS-NC 逃避溶酶体降解的能力，但它们深刻地重塑了感染结核分枝杆菌的巨噬细胞的反应。mRNA 测序显示，由于三甘露糖接枝，近 900 个基因的表达存在差异。出乎意料的是，调节基因的集合富集了参与细胞代谢的途径，特别是氧化磷酸化和糖代谢。
通过在纳米颗粒表面接枝配体来调节细胞代谢的能力，因此可能是重新编程免疫细胞和提高包裹药物疗效的有前途的策略。
