Developmental Exposures to Arsenic: Pneumonia, Immunity, and Microbiomes (DEAPIM)
砷的发育暴露:肺炎、免疫和微生物组 (DEAPIM)
基本信息
- 批准号:10369655
- 负责人:
- 金额:$ 60.45万
- 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:2021-03-10 至 2022-07-31
- 项目状态:已结题
- 来源:
- 关键词:16S ribosomal RNA sequencingAccountingAffectAgeAirAnimal ModelAnimalsAntibody ResponseAntibody titer measurementArsenicB-Cell DevelopmentBangladeshBirthBone MarrowCD4 Positive T LymphocytesCD8-Positive T-LymphocytesCell surfaceCellsCessation of lifeChildChildhoodColorCommunitiesComplexDNA DamageDNA RepairDataDendritic CellsDevelopmentDoseEnvironmental PollutantsExposure toFlow CytometryFoodGenesGoalsGranzymeHealthHospitalizationHumanImmuneImmune systemImmunityImmunologic MarkersImmunology procedureImpairmentIncidenceInfectionLeadLengthLifeLinkLymphocyteMeasuresMediatingMemoryMetagenomicsMorbidity - disease rateMothersOutcomePathway interactionsPeripheral Blood Mononuclear CellPlayPneumococcal vaccinePneumoniaPredispositionPregnancyProductionQuantitative Reverse Transcriptase PCRRegulatory T-LymphocyteResearchResistance to infectionRespiratory Tract InfectionsRiskRoleShotgunsSignal TransductionStreptococcus pneumoniaeT cell differentiationT-Cell ActivationT-Cell DevelopmentT-Cell ProliferationT-LymphocyteT-Lymphocyte SubsetsTestingThymus GlandTimeToxic effectVaccinationVaccinesadaptive immunitybacteriomebooster vaccinecohortcytokinedrinking waterearly life exposureeffector T cellepidemiology studyexposed human populationgenotoxicityglobal healthgut microbiomegut microbiotaimmune functionin uterometagenomic sequencingmicrobialmicrobial communitymicrobiomemicrobiotamonocytemortalityperforinprenatal exposurerespiratoryresponsestem cellsvaccine efficacyvaccine response
项目摘要
ABSTRACT
Exposure of human populations to arsenic via drinking water, air, and food is associated with significant
morbidity and mortality. Along with impairments in immune function, an increased susceptibility to pneumonia
has been observed in children exposed to high levels of arsenic. Pneumonia is a major global health concern
accounting for 70% of pediatric hospitalizations in the US alone. Epidemiological studies indicate a decrease in
the efficacy of respiratory vaccines in arsenic-exposed children. While vaccine efficacy is largely dependent on
host immune function, recent evidence indicates that the gut microbiome may also play a role. However, the
interrelationship of immune function and the microbiome on vaccine response in arsenic-exposed children has
not been studied. It is likely that early exposures to arsenic compromise vaccines protecting against
Streptococcus pneumoniae, the most common bacterial cause of pneumonia. The Scientific Premise is that
Early life and in utero arsenic exposure in children leads to alterations in adaptive immunity via dysregulation of
lymphocyte development and function. The impairment in these immune cells is responsible for decreases in
protection from upper airway infections (such as S. pneumoniae) due to decreased vaccine PCV10 efficacy, as
measured by S. pneumoniae nasopharyngeal (NP) carriage and anti-PCV circulating antibody titers. We also
posit that arsenic disrupts the gut microbiome which may alter vaccine efficacy, due to altered adaptive T cell
development. In Aim 1, we test the hypothesis that arsenic exposure in utero and during early life in children
(1-2 year) leads to (a) impaired PCV10 antibody responses following a booster dose of PCV10, and (b)
influences the NP microbiota diversity and the S. pneumoniae carriage. We will measure PCV10 titers and NP
carriage using qRT-PCR and full length 16s rRNA sequencing. In Aim 2, we test the hypothesis that alterations
in immune function and development are associated with early life arsenic exposure, leading to compromised
host immunity. These measures include PBMC immune biomarkers and functional immune assays including:
a) cell surface markers (CSM = T, B, NK, monocyte/dendritic cells, memory effector T cells) and the Th cell
subsets (Th1, Th2, Th4, Th17, Treg) using 11-color flow cytometry; b) T cell proliferation; c) ex vivo cytokine
production. In Aim 3 we test the hypothesis that differences in functional gut microbial composition are
influenced by immune development and immune function. We will assess the gut bacterial microbiome by
shotgun metagenomics and correlations with; a) PCV10 titers and the pneumococcal carriage (Aim1) and b)
changes in immune markers/function (Aim 2). The study will be conducted among 400 children in Bangladesh
ages between 1 and 2 years. Mothers of the participating children are part of a birth cohort and are followed
throughout their pregnancy, and children are extremely well characterized for arsenic exposure in utero. These
studies will provide new evidence on altered PCV vaccine response and the importance of the gut microbiome
in adverse health outcomes associated with arsenic.
摘要
人类通过饮用水、空气和食物暴露于砷,
发病率和死亡率。沿着免疫功能受损,对肺炎的易感性增加
在暴露于高水平砷的儿童中观察到。肺炎是一个主要的全球健康问题
仅在美国就占儿科住院病例的70%。流行病学研究表明,
呼吸道疫苗在砷暴露儿童中的有效性。虽然疫苗的有效性在很大程度上取决于
宿主的免疫功能,最近的证据表明,肠道微生物组也可能发挥作用。但
砷暴露儿童免疫功能和微生物组对疫苗应答的相互关系,
尚未研究。早期接触砷很可能会损害疫苗的保护作用,
肺炎链球菌是肺炎最常见的细菌。科学假设是,
儿童生命早期和宫内砷暴露通过以下途径导致适应性免疫改变:
淋巴细胞的发育和功能。这些免疫细胞中的损伤是导致
保护免受上呼吸道感染(如S.肺炎),因为疫苗PCV 10效力降低,
测量S。肺炎鼻咽(NP)携带和抗PCV循环抗体滴度。我们也
砷会破坏肠道微生物组,这可能会改变疫苗的效力,因为适应性T细胞
发展在目标1中,我们检验了以下假设:
(1-2年)导致(a)PCV 10加强剂量后PCV 10抗体应答受损,和(B)
影响NP微生物群多样性和S.肺炎携带我们将测量PCV 10滴度和NP
使用qRT-PCR和全长16 s rRNA测序检测载体。在目标2中,我们检验了改变
免疫功能和发育与早期砷暴露有关,
宿主免疫这些措施包括PBMC免疫生物标志物和功能性免疫测定,包括:
a)细胞表面标志物(CSM = T、B、NK、单核细胞/树突细胞、记忆效应T细胞)和Th细胞
使用11色流式细胞术检测T细胞亚群(Th 1、Th 2、Th 4、Th 17、Treg); B)T细胞增殖; c)离体细胞因子
生产在目标3中,我们检验了功能性肠道微生物组成差异的假设,
受免疫发育和免疫功能的影响。我们将评估肠道细菌微生物组,
鸟枪宏基因组学及其与以下各项的相关性:a)PCV 10滴度和肺炎球菌携带(Aim 1)以及B)
免疫标志物/功能的变化(目的2)。这项研究将在孟加拉国的400名儿童中进行
年龄在1到2岁之间。参与儿童的母亲是出生队列的一部分,
在整个怀孕期间,儿童在子宫内接触砷的特征非常明显。这些
研究将为PCV疫苗反应的改变和肠道微生物组的重要性提供新的证据。
与砷有关的不良健康后果。
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 }}
SARAH J BLOSSOM其他文献
SARAH J BLOSSOM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('SARAH J BLOSSOM', 18)}}的其他基金
New Mexico Integrative Science Program Incorporating Research in Environmental Sciences (NM-INSPIRES)
新墨西哥州综合科学计划纳入环境科学研究(NM-INSPIRES)
- 批准号:
10689665 - 财政年份:2022
- 资助金额:
$ 60.45万 - 项目类别:
New Mexico Integrative Science Program Incorporating Research in Environmental Sciences (NM-INSPIRES)
新墨西哥州综合科学计划纳入环境科学研究(NM-INSPIRES)
- 批准号:
10393297 - 财政年份:2022
- 资助金额:
$ 60.45万 - 项目类别:
Developmental Exposures to Arsenic: Pneumonia, Immunity, and Microbiomes (DEAPIM)
砷的发育暴露:肺炎、免疫和微生物组 (DEAPIM)
- 批准号:
10745882 - 财政年份:2022
- 资助金额:
$ 60.45万 - 项目类别:
Epigenetic modulation of CD4+ T cell differentiation and autoimmunity by trichloroethylene
三氯乙烯对 CD4 T 细胞分化和自身免疫的表观遗传调节
- 批准号:
10392944 - 财政年份:2021
- 资助金额:
$ 60.45万 - 项目类别:
Epigenetic modulation of CD4+ T cell differentiation and autoimmunity by trichloroethylene
三氯乙烯对 CD4 T 细胞分化和自身免疫的表观遗传调节
- 批准号:
10115737 - 财政年份:2021
- 资助金额:
$ 60.45万 - 项目类别:
CD4+ T cell-mediated neurotoxicity with continuous trichloroethylene exposure
持续接触三氯乙烯导致 CD4 T 细胞介导的神经毒性
- 批准号:
8755026 - 财政年份:2014
- 资助金额:
$ 60.45万 - 项目类别:
CD4+ T cell-mediated neurotoxicity with continuous trichloroethylene exposure
持续接触三氯乙烯导致 CD4 T 细胞介导的神经毒性
- 批准号:
8926236 - 财政年份:2014
- 资助金额:
$ 60.45万 - 项目类别:
CD4+ T cell-mediated neurotoxicity with continuous trichloroethylene exposure
持续接触三氯乙烯导致 CD4 T 细胞介导的神经毒性
- 批准号:
9067639 - 财政年份:2014
- 资助金额:
$ 60.45万 - 项目类别:
Developmental programming of TCE induced autoimmune disease
TCE诱导的自身免疫性疾病的发育编程
- 批准号:
8927709 - 财政年份:2012
- 资助金额:
$ 60.45万 - 项目类别:
相似海外基金
Unraveling the Dynamics of International Accounting: Exploring the Impact of IFRS Adoption on Firms' Financial Reporting and Business Strategies
揭示国际会计的动态:探索采用 IFRS 对公司财务报告和业务战略的影响
- 批准号:
24K16488 - 财政年份:2024
- 资助金额:
$ 60.45万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Mighty Accounting - Accountancy Automation for 1-person limited companies.
Mighty Accounting - 1 人有限公司的会计自动化。
- 批准号:
10100360 - 财政年份:2024
- 资助金额:
$ 60.45万 - 项目类别:
Collaborative R&D
Accounting for the Fall of Silver? Western exchange banking practice, 1870-1910
白银下跌的原因是什么?
- 批准号:
24K04974 - 财政年份:2024
- 资助金额:
$ 60.45万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
A New Direction in Accounting Education for IT Human Resources
IT人力资源会计教育的新方向
- 批准号:
23K01686 - 财政年份:2023
- 资助金额:
$ 60.45万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
An empirical and theoretical study of the double-accounting system in 19th-century American and British public utility companies
19世纪美国和英国公用事业公司双重会计制度的实证和理论研究
- 批准号:
23K01692 - 财政年份:2023
- 资助金额:
$ 60.45万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
An Empirical Analysis of the Value Effect: An Accounting Viewpoint
价值效应的实证分析:会计观点
- 批准号:
23K01695 - 财政年份:2023
- 资助金额:
$ 60.45万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Accounting model for improving performance on the health and productivity management
提高健康和生产力管理绩效的会计模型
- 批准号:
23K01713 - 财政年份:2023
- 资助金额:
$ 60.45万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
CPS: Medium: Making Every Drop Count: Accounting for Spatiotemporal Variability of Water Needs for Proactive Scheduling of Variable Rate Irrigation Systems
CPS:中:让每一滴水都发挥作用:考虑用水需求的时空变化,主动调度可变速率灌溉系统
- 批准号:
2312319 - 财政年份:2023
- 资助金额:
$ 60.45万 - 项目类别:
Standard Grant
New Role of Not-for-Profit Entities and Their Accounting Standards to Be Unified
非营利实体的新角色及其会计准则将统一
- 批准号:
23K01715 - 财政年份:2023
- 资助金额:
$ 60.45万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Improving Age- and Cause-Specific Under-Five Mortality Rates (ACSU5MR) by Systematically Accounting Measurement Errors to Inform Child Survival Decision Making in Low Income Countries
通过系统地核算测量误差来改善特定年龄和特定原因的五岁以下死亡率 (ACSU5MR),为低收入国家的儿童生存决策提供信息
- 批准号:
10585388 - 财政年份:2023
- 资助金额:
$ 60.45万 - 项目类别: