Department of Microbiology and Immunology, University at Buffalo School of Medicine, Buffalo, New York, USA.
J Infect Dis. 2020 Sep 14;222(8):1363-1370. doi: 10.1093/infdis/jiaa242.
Neutrophils can shape adaptive immunity; however, their role in vaccine-induced protection against infections in vivo remains unclear. Here, we tested their role in the clinically relevant polysaccharide conjugate vaccine against Streptococcus pneumoniae (pneumococcus). We antibody depleted neutrophils during vaccination, allowed them to recover, and 4 weeks later challenged mice with pneumococci. We found that while isotype-treated vaccinated controls were protected against an otherwise lethal infection in naive mice, full protection was lost upon neutrophil depletion. Compared to vaccinated controls, neutrophil-depleted mice had higher lung bacterial burdens, increased incidence of bacteremia, and lower survival rates. Sera from neutrophil-depleted mice had less antipneumococcal IgG2c and IgG3, were less efficient at inducing opsonophagocytic killing of bacteria by neutrophils in vitro, and were worse at protecting naive mice against pneumococcal pneumonia. In summary, neutrophils are required during vaccination for optimal host protection, which has important implications for future vaccine design against pneumococci and other pathogens.
中性粒细胞可以调节适应性免疫；然而，它们在体内疫苗诱导抗感染中的作用尚不清楚。在这里，我们测试了它们在针对肺炎链球菌（肺炎球菌）的临床相关多糖结合疫苗中的作用。我们在接种疫苗期间耗尽中性粒细胞，让它们恢复，4 周后用肺炎球菌感染小鼠。我们发现，虽然同型抗体处理的接种对照在未感染的小鼠中对致命感染有保护作用，但中性粒细胞耗竭后完全丧失了保护作用。与接种对照相比，中性粒细胞耗尽的小鼠肺部细菌负荷更高，菌血症发生率更高，生存率更低。中性粒细胞耗尽的小鼠血清中抗肺炎链球菌 IgG2c 和 IgG3 减少，体外诱导中性粒细胞吞噬杀菌的能力降低，对未感染小鼠的肺炎球菌肺炎的保护作用更差。综上所述，中性粒细胞在接种疫苗时对于宿主的最佳保护是必需的，这对未来针对肺炎球菌和其他病原体的疫苗设计具有重要意义。
