Lu Thea, Porter Adeline R, Kennedy Adam D, Kobayashi Scott D, DeLeo Frank R
Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Mont., USA.
J Innate Immun. 2014;6(5):639-49. doi: 10.1159/000360478. Epub 2014 Apr 5.
Neutrophils are essential for host defense against Staphylococcus aureus infections. Although significant progress has been made, our understanding of neutrophil interactions with S. aureus remains incomplete. To provide a more comprehensive view of this process, we investigated phagocytosis and killing of S. aureus by human neutrophils using varied assay conditions in vitro. A greater percentage of bacteria were internalized by adherent neutrophils compared to those in suspension, and, unexpectedly, uptake of S. aureus by adherent neutrophils occurred efficiently in the absence of opsonins. An antibody specific for S. aureus promoted uptake of unopsonized bacteria in suspension, but had little or no capacity to enhance phagocytosis of S. aureus opsonized with normal human serum or by adherent neutrophils. Collectively, these results indicate that assay conditions can have a significant influence on the phagocytosis and killing of S. aureus by neutrophils. More importantly, the results suggest a vaccine approach directed to enhance opsonophagocytosis alone is not sufficient to promote increased killing of S. aureus by human neutrophils. With the emergence and reemergence of antibiotic-resistant microorganisms, establishing parameters that are optimal for studying neutrophil-S. aureus interactions will pave the way towards developing immune-directed strategies for anti-staphylococcal therapies.
中性粒细胞对于宿主抵御金黄色葡萄球菌感染至关重要。尽管已取得显著进展,但我们对中性粒细胞与金黄色葡萄球菌相互作用的理解仍不完整。为了更全面地了解这一过程,我们在体外使用不同的检测条件研究了人类中性粒细胞对金黄色葡萄球菌的吞噬作用和杀伤作用。与悬浮状态的中性粒细胞相比,贴壁中性粒细胞内化的细菌比例更高,而且出乎意料的是,在没有调理素的情况下,贴壁中性粒细胞对金黄色葡萄球菌的摄取仍能高效发生。一种针对金黄色葡萄球菌的抗体可促进悬浮状态下未被调理的细菌的摄取,但对增强经正常人血清调理或由贴壁中性粒细胞调理的金黄色葡萄球菌的吞噬作用几乎没有能力或没有作用。总体而言,这些结果表明检测条件可对中性粒细胞对金黄色葡萄球菌的吞噬作用和杀伤作用产生重大影响。更重要的是,结果表明仅针对增强调理吞噬作用的疫苗方法不足以促进人类中性粒细胞对金黄色葡萄球菌的杀伤增加。随着抗生素耐药微生物的出现和再次出现,确定研究中性粒细胞与金黄色葡萄球菌相互作用的最佳参数将为开发抗葡萄球菌治疗的免疫导向策略铺平道路。