PATHOGENESIS OF INTESTINAL DYSFUNCTION IN SIMIAN AIDS
猿猴艾滋病肠功能障碍的发病机制
基本信息
- 批准号:8357341
- 负责人:
- 金额:$ 9.57万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-05-01 至 2012-04-30
- 项目状态:已结题
- 来源:
- 关键词:Animal ModelAutologousCD4 Positive T LymphocytesCaliforniaCell CountChronicColorEvaluationFlow CytometryFunctional disorderFundingGene ExpressionGenomicsGrantGut associated lymphoid tissueHIV InfectionsHIV-1HomingImmune systemIndividualIntestinesKineticsLeadLymphocyteMacaca mulattaMaintenanceMethodologyModelingMolecularMucous MembraneNational Center for Research ResourcesPathogenesisPeripheralPrimatesPrincipal InvestigatorProcessResearchResearch InfrastructureResearch ProposalsResourcesSIVSimian Acquired Immunodeficiency SyndromeSourceT-Cell DepletionT-LymphocyteUnited States National Institutes of HealthViralVirus DiseasesVirus Replicationantiretroviral therapybasecostexperienceimmune functionin vivoinsightlymph nodesmolecular imagingmucosal siteperipheral bloodpinacolyl methylphosphonic acidrestoration
项目摘要
This subproject is one of many research subprojects utilizing the resources
provided by a Center grant funded by NIH/NCRR. Primary support for the subproject
and the subproject's principal investigator may have been provided by other sources,
including other NIH sources. The Total Cost listed for the subproject likely
represents the estimated amount of Center infrastructure utilized by the subproject,
not direct funding provided by the NCRR grant to the subproject or subproject staff.
The efficacy of antiretroviral therapy (ART) in HIV-1 infected individuals is determined by restoration of peripheral blood CD4+ T cell numbers and viral suppression. However, peripheral blood represents only 2% of the total lymphocytes in the body. In contrast, gut associated lymphoid tissue (GALT) harbors 80% of the lymphocytes in the body. Our previous studies showed that severe CD4+ T cell depletion occurs in GALT during primary HIV infection and that CD4+ T cell restoration in GALT is modest and slow compared to peripheral blood during ART. These changes in GALT are not adequately reflected in peripheral blood analysis. The kinetics and mechanisms of CD4+ T cell restoration and function in GALT following ART have not been fully determined. Simian immunodeficiency virus (SIV) infected rhesus macaques provide an excellent animal model to study the gut mucosal immune system in comparison to peripheral blood compartment. The overall objective of this research proposal is to examine the suppression of viral replication and kinetics and mechanisms of restoration of gut mucosal immune system and function in comparison to mucosal and peripheral lymph nodes and peripheral blood in rhesus macaques starting ART (combination of PMPA and FTC) during primary or chronic SIV infection. Our hypothesis is that slow restoration of CD4+ T cells in GALT during therapy can be attributed to the disruption of the functional organization of the gut mucosal tissue occurring very early in SIV infection and this may not adequately support survival and maintenance of the CD4+ T cells homing to gut mucosa. Longitudinal evaluation in the SIV model will lead to characterization of the mechanisms and relationship between CD4+ T cell restoration in GALT, peripheral blood, and lymph node compartments (peripheral, and those draining mucosal sites). There are 3 specific aims. In rhesus macaques initiating ART during primary or chronic SIV infection, (1) to determine suppression of SIV replication and genomic diversity, and the kinetics of CD4+ T cell restoration in GALT in comparison to peripheral blood and lymph nodes; (2) to determine the homing and survival of CD4+ T cells in the GALT microenvironment and (3) to investigate the molecular processes involved in the restoration of gut mucosal immune system. The proposal capitalizes on our experience in enteropathogenic studies in the SIV model, expertise in multi-color flow cytometry, in vivo molecular imaging, autologous T cell transfer and gene expression methodologies. The proposed studies promise to provide valuable insights into the impact of impaired gut microenvironment on the viral suppression and restoration of gut mucosal immune system compared to mucosal and peripheral lymph node compartments, and molecular basis of pathophysiologic processes in GALT.
这个子项目是利用这些资源的众多研究子项目之一
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)
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Satya Dandekar其他文献
Satya Dandekar的其他文献
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{{ truncateString('Satya Dandekar', 18)}}的其他基金
Molecules and Pathways at the Coccidioides Host-Pathogen Interface
球孢子菌宿主-病原体界面的分子和途径
- 批准号:
10364963 - 财政年份:2022
- 资助金额:
$ 9.57万 - 项目类别:
Immune and metabolic correlates of Coccidioides disease spectrum and outcomes
球孢子菌疾病谱和结果的免疫和代谢相关性
- 批准号:
10540815 - 财政年份:2022
- 资助金额:
$ 9.57万 - 项目类别:
Molecules and Pathways at the Coccidioides Host-Pathogen Interface
球孢子菌宿主-病原体界面的分子和途径
- 批准号:
10540795 - 财政年份:2022
- 资助金额:
$ 9.57万 - 项目类别:
Immune and metabolic correlates of Coccidioides disease spectrum and outcomes
球孢子菌疾病谱和结果的免疫和代谢相关性
- 批准号:
10364969 - 财政年份:2022
- 资助金额:
$ 9.57万 - 项目类别:
"Corral and Kill" strategy for HIV eradication using MSC in an SIV model
在 SIV 模型中使用 MSC 根除 HIV 的“围堵和杀死”策略
- 批准号:
10023879 - 财政年份:2020
- 资助金额:
$ 9.57万 - 项目类别:
"Corral and Kill" strategy for HIV eradication using MSC in an SIV model
在 SIV 模型中使用 MSC 根除 HIV 的“围堵和杀死”策略
- 批准号:
10368941 - 财政年份:2020
- 资助金额:
$ 9.57万 - 项目类别:
"Corral and Kill" strategy for HIV eradication using MSC in an SIV model
在 SIV 模型中使用 MSC 根除 HIV 的“围堵和杀死”策略
- 批准号:
10579905 - 财政年份:2020
- 资助金额:
$ 9.57万 - 项目类别:
Early HIV Effects on Gut Immunity and Inflammation for Seeding Viral Reservoirs
早期艾滋病毒对肠道免疫和炎症的影响,以播种病毒库
- 批准号:
9154447 - 财政年份:2016
- 资助金额:
$ 9.57万 - 项目类别:
33rd Annual Symposium on NHP Models for AIDS
第 33 届 NHP 艾滋病模型年度研讨会
- 批准号:
9065384 - 财政年份:2015
- 资助金额:
$ 9.57万 - 项目类别:
INTESTINAL CYTOKINE AND T CELL HEMEOSTASIS IN SIV INFECTION
SIV 感染中的肠道细胞因子和 T 细胞止血作用
- 批准号:
8357367 - 财政年份:2011
- 资助金额:
$ 9.57万 - 项目类别:
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