Department of Medicine, School of Medicine, University of Louisville, Louisville, KY, USA.
Microbiology & Immunology, School of Medicine, University of Louisville, Louisville, KY, USA.
Cell Microbiol. 2018 Jun;20(6):e12829. doi: 10.1111/cmi.12829. Epub 2018 Feb 12.
Filifactor alocis is a newly appreciated pathogen in periodontal diseases. Neutrophils are the predominant innate immune cell in the gingival crevice. In this study, we examined modulation of human neutrophil antimicrobial functions by F. alocis. Both non-opsonised and serum-opsonised F. alocis were engulfed by neutrophils but were not efficiently eliminated. Challenge of neutrophils with either non-opsonised or serum-opsonised F. alocis induced a minimal intracellular as well as extracellular respiratory burst response compared to opsonised Staphylococcus aureus and fMLF, respectively. However, pretreatment or simultaneous challenge of neutrophils with F. alocis did not affect the subsequent oxidative response to a particulate stimulus, suggesting that the inability to trigger the respiratory response was only localised to F. alocis phagosomes. In addition, although neutrophils engulfed live or heat-killed F. alocis with the same efficiency, heat-killed F. alocis elicited a higher intracellular respiratory burst response compared to viable organisms, along with decreased surface expression of CD35, a marker of secretory vesicles. F. alocis phagosomes remained immature by delayed and reduced recruitment of specific and azurophil granules, respectively. These results suggest that F. alocis withstands neutrophil antimicrobial responses by preventing intracellular ROS production, along with specific and azurophil granule recruitment to the bacterial phagosome.
栖牙密螺旋体是一种新发现的牙周病病原体。中性粒细胞是龈沟中主要的先天免疫细胞。在本研究中,我们研究了栖牙密螺旋体对人中性粒细胞抗菌功能的调节。未调理和血清调理的栖牙密螺旋体均被中性粒细胞吞噬,但不能有效清除。与调理的金黄色葡萄球菌和 fMLF 相比,用未调理或血清调理的栖牙密螺旋体刺激中性粒细胞,分别引起最小的细胞内和细胞外呼吸爆发反应。然而,用栖牙密螺旋体预处理或同时刺激中性粒细胞不会影响随后对颗粒性刺激物的氧化反应,这表明不能触发呼吸反应仅局限于栖牙密螺旋体吞噬体。此外,尽管中性粒细胞以相同的效率吞噬活的或热杀死的栖牙密螺旋体,但与活生物体相比,热杀死的栖牙密螺旋体引起更高的细胞内呼吸爆发反应,同时表面表达 CD35 的减少,这是分泌囊泡的标志物。栖牙密螺旋体吞噬体通过分别延迟和减少特异性和嗜中性粒细胞颗粒的募集而保持不成熟。这些结果表明,栖牙密螺旋体通过防止细胞内 ROS 产生以及特异性和嗜中性粒细胞颗粒募集到细菌吞噬体,从而抵抗中性粒细胞的抗菌反应。