Zhang Xiaohuan, Zhao Sainan, Sun Luping, Li Wenqing, Wei Qiao, Ashman Robert B, Hu Yan
Department of Oral Biology, Guanghua School of Stomatology, Sun Yat-sen University Guangzhou, China.
Department of Oral Biology, Guanghua School of Stomatology, Sun Yat-sen UniversityGuangzhou, China; Affiliated Hospital of Shandong University of Traditional Chinese MedicineJinan, China.
Am J Transl Res. 2017 Jan 15;9(1):50-62. eCollection 2017.
is an important opportunistic fungus causing both disseminated and local infections. The discovery of neutrophil extracellular traps (NETs) has presented a new strategy to kill microorganisms in host's innate immune response. Although it has been reported that NETs can trap and kill both yeast and hyphal forms of , the mechanism by which escape from NETs has not been fully understood. In this study, the ability of two strains of SC5314 and 3683 to escape NETs-mediated killing was compared. It was found that SC5314 induced higher levels of reactive oxygen species (ROS) and expressions of Rac1/2 and more NETs formation by neutrophils, and also generated more deoxyribonucleases (DNase) than 3683 did. However, resistance to neutrophils killing was greater in SC5314 than that of 3683. When extracellular traps were degraded by exogenous DNase I or catalase, and neutrophil phagocytic activity blocked by cytochalasin D, the killing capacity of neutrophils co-cultured with either SC5314 or 3683 was significantly decreased. This study indicates that can escape from the trapping and killing of NETs by secreting DNase, which offers further insights into the basis for differences in virulence of different strains of .
是一种重要的机会性真菌,可引起播散性感染和局部感染。中性粒细胞胞外陷阱(NETs)的发现为宿主固有免疫反应中杀灭微生物提供了一种新策略。尽管已有报道称NETs可捕获并杀死的酵母和菌丝形态,但从NETs中逃脱的机制尚未完全明确。在本研究中,比较了两株白色念珠菌SC5314和3683逃脱NETs介导杀伤的能力。结果发现,SC5314诱导中性粒细胞产生更高水平的活性氧(ROS)、Rac1/2表达以及更多的NETs形成,并且比3683产生更多的脱氧核糖核酸酶(DNase)。然而,SC5314对中性粒细胞杀伤的抗性比3683更强。当用外源性DNase I或过氧化氢酶降解细胞外陷阱,并用细胞松弛素D阻断中性粒细胞吞噬活性时,与SC5314或3683共培养的中性粒细胞的杀伤能力显著降低。本研究表明,白色念珠菌可通过分泌DNase从NETs的捕获和杀伤中逃脱,这为不同菌株毒力差异的基础提供了进一步的见解。