The role of neutrophils in the age-driven decline in anti-pneumococcal vaccine responses
中性粒细胞在年龄驱动的抗肺炎球菌疫苗反应下降中的作用
基本信息
- 批准号:10359412
- 负责人:
- 金额:$ 8.05万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-06-15 至 2021-09-29
- 项目状态:已结题
- 来源:
- 关键词:AffectAgeAgingAnti-Bacterial AgentsAntibodiesAntibody FormationAntibody ResponseAntigen-Presenting CellsAutomobile DrivingB-LymphocytesBacteriaBacterial PneumoniaCD4 Positive T LymphocytesCell physiologyCellsClinicalCoculture TechniquesCommunitiesDataEconomic BurdenElderlyFutureGoalsHost DefenseHost resistanceHumanHuman VolunteersImmuneImmune SeraImpairmentIn VitroIndividualInfectionInnate Immune ResponseLinkMeasuresMediatingMediator of activation proteinMemoryMissionMusNatural ImmunityPathway interactionsPhenotypePlayPneumococcal InfectionsPneumococcal conjugate vaccinePneumococcal vaccinePneumoniaPopulationPredispositionPrevnarRoleShapesSiteStreptococcus pneumoniaeT cell responseT-LymphocyteTestingTimeVaccinatedVaccinationVaccinesWorkadaptive immunityage groupage relatedagedantimicrobialclinically relevantcommunity acquired pneumoniadesignefficacy evaluationhealth economicshealthy agingimmunosenescencein vivoinnovationmouse modelneutrophilnovelpathogenrecruitresponsetranscriptome sequencingvaccine accessvaccine efficacyvaccine response
项目摘要
ABSTRACT
Despite the availability of vaccines, Streptococcus pneumoniae (pneumococcus) infections in the elderly
remain a health and economic burden in the USA. This calls for a better understanding of pathways driving
immune dysregulation in aged hosts, reducing vaccine efficacy and rendering this population susceptible to
infections. Our long-term goal is to elucidate the role of polymorphonuclear leukocytes (PMN) in the age-
driven reduction in vaccine responses and increased susceptibility to S. pneumoniae infection. Background:
A key immune cell following S. pneumoniae infection is PMN. PMNs are innate cells required for controlling
bacterial numbers and whose function is known to decline with age. Recent work shows that PMNs are
important regulators of adaptive immunity. However, the role of PMNs in clinically relevant vaccinations and
their impact in the reduced vaccine efficacy seen in aging remains completely unexplored. We found that
vaccination with the pneumococcal conjugate vaccine Prevnar-13, failed to protect old mice against
pneumococcal infection. Further, in young hosts, optimal protection following vaccination required PMNs both
at the time vaccine administration and at the time of pneumococcal-challenge, highlighting the role of PMNs as
both inducers and effectors of vaccine responses. This led to the Hypothesis that age-driven changes in
PMNs result in the decline of vaccine efficacy against S. pneumoniae in the elderly. Here we test this
hypothesis in both murine models and human volunteers with the following Aims: 1) Test the role of PMNs as
effectors in the decline of pneumococcal vaccine efficacy during aging. 2) Test the role of PMNs as inducers of
the age-driven decline in pneumococcal vaccine efficacy. 3) Test the effect of host aging on PMN responses
following vaccination in human donors. Significance/ innovation: Elucidating the role of PMNs in the decline
in vaccine efficacy against pneumococci in the elderly will vastly contribute to our understanding of how aging
alters innate immune responses and how innate immunity in turn regulates the decline in adaptive memory
responses. Further, understanding the role of PMNs, which are involved in host defense against multiple
pathogens, is imperative for future design of better preventative approaches against pneumococci and other
relevant infections that target the vulnerable elderly population. This proposal is perfectly in line with NIA’s
mission to promote healthy aging.
摘要
尽管有疫苗,但老年人肺炎链球菌(肺炎球菌)感染
这是美国的健康和经济负担。这就需要更好地理解驾驶的途径
老年宿主的免疫失调,降低疫苗效力,使这一群体易受
感染.我们的长期目标是阐明多形核白细胞(PMN)在年龄-
导致疫苗应答减少和对沙门氏菌的易感性增加。肺炎感染。工作背景:
一个关键的免疫细胞继S。肺炎感染是中性粒细胞。中性粒细胞是先天性细胞,
细菌数量和其功能是众所周知的下降与年龄。最近的研究表明,PMNs
重要的适应性免疫调节因子。然而,中性粒细胞在临床相关疫苗接种中的作用,
它们在老化中所见的疫苗效力降低中的影响仍然完全未被探索。我们发现
接种肺炎球菌结合疫苗Prevnar-13,未能保护老年小鼠免受
肺炎球菌感染此外,在年轻宿主中,接种疫苗后的最佳保护需要PMNs,
在接种疫苗和肺炎球菌攻毒时,强调了中性粒细胞作为
疫苗应答的诱导剂和效应剂。这导致了一个假设,即年龄驱动的变化,
PMNs可导致疫苗对S.老年人的肺炎我们来测试一下
在小鼠模型和人类志愿者中的假设具有以下目的:1)测试PMNs作为
在老化过程中肺炎球菌疫苗效力下降的影响因素。2)测试中性粒细胞作为诱导剂的作用
年龄驱动的肺炎球菌疫苗功效下降。3)测试宿主老化对PMN反应的影响
在人类捐赠者中接种疫苗后。意义/创新:阐明PMNs在下降中的作用
疫苗对老年人肺炎球菌的有效性将极大地有助于我们理解衰老是如何
改变先天免疫反应以及先天免疫如何反过来调节适应性记忆的下降
应答此外,了解PMNs的作用,这是参与主机防御多个
病原体,对于未来设计更好的预防肺炎球菌和其他病原体的方法至关重要。
针对脆弱老年人的相关感染。这一建议完全符合NIA的
促进健康老龄化的使命。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Elsa Bou Ghanem其他文献
Elsa Bou Ghanem的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Elsa Bou Ghanem', 18)}}的其他基金
The role of PMNs and CD73 in host-resistance against S. pneumoniae / influenza A virus co-infection
PMNs和CD73在宿主抵抗肺炎链球菌/甲型流感病毒混合感染中的作用
- 批准号:
10652758 - 财政年份:2023
- 资助金额:
$ 8.05万 - 项目类别:
The role of neutrophils in the age-driven decline in anti-pneumococcal vaccine responses
中性粒细胞在年龄驱动的抗肺炎球菌疫苗反应下降中的作用
- 批准号:
10655642 - 财政年份:2021
- 资助金额:
$ 8.05万 - 项目类别:
The role of neutrophils in the age-driven decline in anti-pneumococcal vaccine responses
中性粒细胞在年龄驱动的抗肺炎球菌疫苗反应下降中的作用
- 批准号:
10209125 - 财政年份:2021
- 资助金额:
$ 8.05万 - 项目类别:
The efficacy of Liposomal Encapsulation of Polysaccharides pneumococcal vaccine in protecting aged hosts against invasive Streptococcus pneumoniae infections in murine models
脂质体封装多糖肺炎球菌疫苗在小鼠模型中保护老年宿主免受侵袭性肺炎链球菌感染的功效
- 批准号:
9806492 - 财政年份:2019
- 资助金额:
$ 8.05万 - 项目类别:
The role of extracellular adenosine in age-driven susceptibility to S. pneumoniae lung infection
细胞外腺苷在年龄驱动的肺炎链球菌肺部感染易感性中的作用
- 批准号:
9793990 - 财政年份:2018
- 资助金额:
$ 8.05万 - 项目类别:
The role of extracellular adenosine in age-driven susceptibility to S. pneumoniae lung infection
细胞外腺苷在年龄驱动的肺炎链球菌肺部感染易感性中的作用
- 批准号:
9270486 - 财政年份:2016
- 资助金额:
$ 8.05万 - 项目类别:
The role of extracellular adenosine in age-driven susceptibility to S. pneumoniae lung infection
细胞外腺苷在年龄驱动的肺炎链球菌肺部感染易感性中的作用
- 批准号:
9013783 - 财政年份:2016
- 资助金额:
$ 8.05万 - 项目类别:
相似国自然基金
靶向递送一氧化碳调控AGE-RAGE级联反应促进糖尿病创面愈合研究
- 批准号:JCZRQN202500010
- 批准年份:2025
- 资助金额:0.0 万元
- 项目类别:省市级项目
对香豆酸抑制AGE-RAGE-Ang-1通路改善海马血管生成障碍发挥抗阿尔兹海默病作用
- 批准号:2025JJ70209
- 批准年份:2025
- 资助金额:0.0 万元
- 项目类别:省市级项目
AGE-RAGE通路调控慢性胰腺炎纤维化进程的作用及分子机制
- 批准号:
- 批准年份:2024
- 资助金额:0 万元
- 项目类别:面上项目
甜茶抑制AGE-RAGE通路增强突触可塑性改善小鼠抑郁样行为
- 批准号:2023JJ50274
- 批准年份:2023
- 资助金额:0.0 万元
- 项目类别:省市级项目
蒙药额尔敦-乌日勒基础方调控AGE-RAGE信号通路改善术后认知功能障碍研究
- 批准号:
- 批准年份:2022
- 资助金额:33 万元
- 项目类别:地区科学基金项目
补肾健脾祛瘀方调控AGE/RAGE信号通路在再生障碍性贫血骨髓间充质干细胞功能受损的作用与机制研究
- 批准号:
- 批准年份:2022
- 资助金额:52 万元
- 项目类别:面上项目
LncRNA GAS5在2型糖尿病动脉粥样硬化中对AGE-RAGE 信号通路上相关基因的调控作用及机制研究
- 批准号:n/a
- 批准年份:2022
- 资助金额:10.0 万元
- 项目类别:省市级项目
围绕GLP1-Arginine-AGE/RAGE轴构建探针组学方法探索大柴胡汤异病同治的效应机制
- 批准号:81973577
- 批准年份:2019
- 资助金额:55.0 万元
- 项目类别:面上项目
AGE/RAGE通路microRNA编码基因多态性与2型糖尿病并发冠心病的关联研究
- 批准号:81602908
- 批准年份:2016
- 资助金额:18.0 万元
- 项目类别:青年科学基金项目
高血糖激活滑膜AGE-RAGE-PKC轴致骨关节炎易感的机制研究
- 批准号:81501928
- 批准年份:2015
- 资助金额:18.0 万元
- 项目类别:青年科学基金项目
相似海外基金
The Phenomenon of Stem Cell Aging according to Methylation Estimates of Age After Hematopoietic Stem Cell Transplantation
根据造血干细胞移植后甲基化年龄估算干细胞衰老现象
- 批准号:
23K07844 - 财政年份:2023
- 资助金额:
$ 8.05万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Analysis of Age-dependent Functional Changes in Skeletal Muscle CB1 Receptors by an in Vitro Model of Aging-related Muscle Atrophy
通过衰老相关性肌肉萎缩的体外模型分析骨骼肌 CB1 受体的年龄依赖性功能变化
- 批准号:
22KJ2960 - 财政年份:2023
- 资助金额:
$ 8.05万 - 项目类别:
Grant-in-Aid for JSPS Fellows
Joint U.S.-Japan Measures for Aging and Dementia Derived from the Prevention of Age-Related and Noise-induced Hearing Loss
美日针对预防与年龄相关和噪声引起的听力损失而导致的老龄化和痴呆症联合措施
- 批准号:
23KK0156 - 财政年份:2023
- 资助金额:
$ 8.05万 - 项目类别:
Fund for the Promotion of Joint International Research (International Collaborative Research)
The Effects of Muscle Fatigability on Gait Instability in Aging and Age-Related Falls Risk
肌肉疲劳对衰老步态不稳定性和年龄相关跌倒风险的影响
- 批准号:
10677409 - 财政年份:2023
- 资助金额:
$ 8.05万 - 项目类别:
Characterizing gut physiology by age, frailty, and sex: assessing the role of the aging gut in "inflamm-aging"
按年龄、虚弱和性别表征肠道生理学特征:评估衰老肠道在“炎症衰老”中的作用
- 批准号:
497927 - 财政年份:2023
- 资助金额:
$ 8.05万 - 项目类别:
Role of AGE/RAGEsignaling as a driver of pathological aging in the brain
AGE/RAGE信号传导作为大脑病理性衰老驱动因素的作用
- 批准号:
10836835 - 财政年份:2023
- 资助金额:
$ 8.05万 - 项目类别:
Deciphering the role of osteopontin in the aging eye and age-related macular degeneration
破译骨桥蛋白在眼睛老化和年龄相关性黄斑变性中的作用
- 批准号:
10679287 - 财政年份:2023
- 资助金额:
$ 8.05万 - 项目类别:
Elucidation of the protein kinase NLK-mediated aging mechanisms and treatment of age-related diseases
阐明蛋白激酶NLK介导的衰老机制及年龄相关疾病的治疗
- 批准号:
23K06378 - 财政年份:2023
- 资助金额:
$ 8.05万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Underlying mechanisms of age-related changes in ingestive behaviors: From the perspective of the aging brain and deterioration of the gustatory system.
与年龄相关的摄入行为变化的潜在机制:从大脑老化和味觉系统退化的角度来看。
- 批准号:
23K10845 - 财政年份:2023
- 资助金额:
$ 8.05万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Targeting Age-Activated Proinflammatory Chemokine Signaling by CCL2/11 to Enhance Skeletal Muscle Regeneration in Aging
通过 CCL2/11 靶向年龄激活的促炎趋化因子信号传导以增强衰老过程中的骨骼肌再生
- 批准号:
478877 - 财政年份:2023
- 资助金额:
$ 8.05万 - 项目类别:
Operating Grants