The Age-Driven Decline in Neutrophil Function Contributes to the Reduced Efficacy of the Pneumococcal Conjugate Vaccine in Old Hosts.
The Age-Driven Decline in Neutrophil Function Contributes to the Reduced Efficacy of the Pneumococcal Conjugate Vaccine in Old Hosts.
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DOI：
10.3389/fcimb.2022.849224
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发表时间：
2022
影响因子：
5.7
通讯作者：
Bou Ghanem EN
中科院分区：
文献类型：
--
作者：
Simmons SR;Tchalla EYI;Bhalla M;Bou Ghanem EN
尽管疫苗的可用性，肺炎链球菌（肺炎球菌）仍然是老年人感染的一个严重原因。抗肺炎球菌疫苗的有效性随着年龄的增长而下降。虽然年龄驱动的抗体应答变化是明确的，但对先天免疫细胞如多形核白细胞（PMN）在衰老中观察到的疫苗保护作用降低中的作用知之甚少。在这里，我们探讨了中性粒细胞在保护S。接种宿主中的肺炎。我们发现肺炎球菌结合疫苗（PCV）处理的幼鼠在用S.肺炎杆菌导致宿主对感染的保护的急剧丧失。免疫增强了中性粒细胞对沙门氏菌的杀伤能力。肺炎，这取决于抗体对细菌的调理作用。免疫血清的细菌调理作用增加了几种PMN抗微生物活性，包括细菌摄取、脱粒和ROS产生。正如预期的那样，PCV未能保护老年小鼠免受S。肺炎。在探讨中性粒细胞在这种受损的保护作用，我们发现，老化是伴随着中性粒细胞功能的内在下降。老年小鼠的中性粒细胞不能有效地杀死S。即使当细菌用来自年轻对照的免疫血清调理时，在探索机制时，我们发现来自老年小鼠的PMNs产生较少的抗菌肽CRAMP，并且未能有效地杀死吞噬的肺炎球菌。重要的是，过继转移的PMNs从年轻的小鼠逆转了接种疫苗的老年小鼠对肺炎球菌感染的易感性。总体而言，这项研究表明，年龄驱动的PMN功能下降损害疫苗介导的对肺炎链球菌的保护。
Despite the availability of vaccines, Streptococcus pneumoniae (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 S. pneumoniae in vaccinated hosts. We found that depletion of PMNs in pneumococcal conjugate vaccine (PCV) treated young mice prior to pulmonary challenge with S. pneumoniae resulted in dramatic loss of host protection against infection. Immunization boosted the ability of PMNs to kill S. pneumoniae 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 S. pneumoniae. 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 S. pneumoniae 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 Streptococcus pneumoniae.