Duszenko Nikolas, van Willigen Danny M, Welling Mick M, de Korne Clarize M, van Schuijlenburg Roos, Winkel Beatrice M F, van Leeuwen Fijs W B, Roestenberg Meta
Department of Parasitology, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands.
Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands.
ACS Infect Dis. 2020 Jul 10;6(7):1734-1744. doi: 10.1021/acsinfecdis.9b00523. Epub 2020 May 15.
In an era of antimicrobial resistance, a better understanding of the interaction between bacteria and the sentinel immune system is needed to discover new therapeutic targets for combating bacterial infectious disease. Sentinel immune cells such as macrophages phagocytose intact bacteria and thereby initiate ensuing immune responses. The bacterial surface composition is a key element that determines the macrophage signaling. To study the role of the bacterial cell surface composition in immune recognition, we developed a platform technology for altering bacterial surfaces in a controlled manner with versatile chemical scaffolds. We show that these scaffolds are efficiently loaded onto both Gram-positive and -negative bacteria and that their presence does not impair the capacity of monocyte-derived macrophages to phagocytose bacteria and subsequently signal to other components of the immune system. We believe this technology thus presents a useful tool to study the role of bacterial cell surface composition in disease etiology and potentially in novel interventions utilizing intact bacteria for vaccination.
在抗菌药物耐药性的时代，需要更好地了解细菌与哨兵免疫系统之间的相互作用，以发现对抗细菌感染性疾病的新治疗靶点。巨噬细胞等哨兵免疫细胞吞噬完整细菌，从而引发后续免疫反应。细菌表面组成是决定巨噬细胞信号传导的关键因素。为了研究细菌细胞表面组成在免疫识别中的作用，我们开发了一种平台技术，用多功能化学支架以可控方式改变细菌表面。我们表明，这些支架能有效负载到革兰氏阳性菌和阴性菌上，且它们的存在不会损害单核细胞衍生的巨噬细胞吞噬细菌并随后向免疫系统其他成分发出信号的能力。我们认为，这项技术因此为研究细菌细胞表面组成在疾病病因学中的作用以及潜在地在利用完整细菌进行疫苗接种的新型干预措施中提供了一个有用的工具。
