Instituto de Investigación Valdecilla IDIVAL, Santander, 39011, Spain.
Servicio de Microbiología, Hospital Universitario Marqués de Valdecilla, Santander, 39008, Spain.
Sci Rep. 2017 Jul 4;7(1):4571. doi: 10.1038/s41598-017-04870-8.
Acinetobacter baumannii is a common cause of health care associated infections worldwide. A. pittii is an opportunistic pathogen also frequently isolated from Acinetobacter infections other than those from A. baumannii. Knowledge of Acinetobacter virulence factors and their role in pathogenesis is scarce. Also, there are no detailed published reports on the interactions between A. pittii and human phagocytic cells. Using confocal laser and scanning electron microscopy, immunofluorescence, and live-cell imaging, our study shows that immediately after bacteria-cell contact, neutrophils rapidly and continuously engulf and kill bacteria during at least 4 hours of infection in vitro. After 3 h of infection, neutrophils start to release neutrophil extracellular traps (NETs) against Acinetobacter. DNA in NETs colocalizes well with human histone H3 and with the specific neutrophil elastase. We have observed that human neutrophils use large filopodia as cellular tentacles to sense local environment but also to detect and retain bacteria during phagocytosis. Furthermore, co-cultivation of neutrophils with human differentiated macrophages before infections shows that human neutrophils, but not macrophages, are key immune cells to control Acinetobacter. Although macrophages were largely activated by both bacterial species, they lack the phagocytic activity demonstrated by neutrophils.
鲍曼不动杆菌是全球引起医源性感染的常见病原体。洋葱伯克霍尔德菌是一种机会致病菌,除了从鲍曼不动杆菌感染中分离出来之外,还经常从其他不动杆菌感染中分离出来。关于不动杆菌的毒力因子及其在发病机制中的作用的知识还很缺乏。此外,目前还没有关于洋葱伯克霍尔德菌与人类吞噬细胞之间相互作用的详细报道。通过共聚焦激光扫描电子显微镜、免疫荧光和活细胞成像,我们的研究表明,在体外感染至少 4 小时内,中性粒细胞在与细菌接触后迅速、连续地吞噬并杀死细菌。感染 3 小时后,中性粒细胞开始针对不动杆菌释放中性粒细胞胞外诱捕网(NETs)。NETs 中的 DNA 与人组蛋白 H3 和特定的中性粒细胞弹性蛋白酶很好地共定位。我们观察到,人类中性粒细胞使用大的丝状伪足作为细胞触须,以感知局部环境,但也在吞噬过程中检测和保留细菌。此外,在感染前将中性粒细胞与人类分化的巨噬细胞共培养表明,中性粒细胞而非巨噬细胞是控制不动杆菌的关键免疫细胞。尽管两种细菌都能使巨噬细胞大量激活,但它们缺乏中性粒细胞所表现出的吞噬活性。