Department of Microbiology and Immunology, University at Buffalo School of Medicine, Buffalo, NY, United States.
Front Cell Infect Microbiol. 2022 Mar 23;12:849224. doi: 10.3389/fcimb.2022.849224. eCollection 2022.
Despite the availability of vaccines, (pneumococcus) remains a serious cause of infections in the elderly. The efficacy of anti-pneumococcal vaccines declines with age. While age-driven changes in antibody responses are well defined, less is known about the role of innate immune cells such as polymorphonuclear leukocytes (PMNs) in the reduced vaccine protection seen in aging. Here we explored the role of PMNs in protection against in vaccinated hosts. We found that depletion of PMNs in pneumococcal conjugate vaccine (PCV) treated young mice prior to pulmonary challenge with resulted in dramatic loss of host protection against infection. Immunization boosted the ability of PMNs to kill and this was dependent on bacterial opsonization by antibodies. Bacterial opsonization with immune sera increased several PMN anti-microbial activities including bacterial uptake, degranulation and ROS production. As expected, PCV failed to protect old mice against . In probing the role of PMNs in this impaired protection, we found that aging was accompanied by an intrinsic decline in PMN function. PMNs from old mice failed to effectively kill even when the bacteria were opsonized with immune sera from young controls. In exploring mechanisms, we found that PMNs from old mice produced less of the antimicrobial peptide CRAMP and failed to efficiently kill engulfed pneumococci. Importantly, adoptive transfer of PMNs from young mice reversed the susceptibility of vaccinated old mice to pneumococcal infection. Overall, this study demonstrates that the age-driven decline in PMN function impairs vaccine-mediated protection against .
尽管有疫苗可用，但肺炎球菌仍然是老年人感染的严重原因。抗肺炎球菌疫苗的功效随着年龄的增长而下降。虽然年龄相关的抗体反应变化已经得到很好的定义，但对于先天免疫细胞（如多形核白细胞[PMN]）在衰老过程中疫苗保护作用降低的作用知之甚少。在这里，我们探讨了 PMN 在接种宿主抵抗肺炎球菌中的作用。我们发现，在肺炎球菌结合疫苗（PCV）治疗的年轻小鼠中，在肺部受到肺炎球菌侵袭之前消耗 PMN，会导致宿主对感染的保护作用明显丧失。免疫接种增强了 PMN 杀死肺炎球菌的能力，这依赖于抗体对细菌的调理作用。用免疫血清调理细菌增加了 PMN 的几种抗微生物活性，包括细菌摄取、脱颗粒和 ROS 产生。正如预期的那样，PCV 未能保护老年小鼠免受感染。在探究 PMN 在这种受损保护中的作用时，我们发现衰老伴随着 PMN 功能的内在下降。即使使用来自年轻对照的免疫血清调理细菌，老年小鼠的 PMN 也无法有效杀死肺炎球菌。在探讨机制时，我们发现老年小鼠的 PMN 产生的抗菌肽 CRAMP 较少，并且无法有效杀死吞噬的肺炎球菌。重要的是，从年轻小鼠中过继转移 PMN 可逆转接种疫苗的老年小鼠对肺炎球菌感染的易感性。总的来说，这项研究表明，PMN 功能的年龄相关下降会损害疫苗介导的对肺炎球菌的保护作用。
