Macrophages, Granulomas, and Bacterial Persistence
Macrophages, Granulomas, and Bacterial Persistence
批准号:
9277403
负责人:
Corrella S Detweiler
金额:
$23.1万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
已结题
起止时间:
2016-06-01 至 2019-05-31
关键词:
AcuteAddressAlpha CellAreaBacteriaBacterial InfectionsBone MarrowBrucella abortusCell SurvivalCharacteristicsChemicalsChronicChronic DiseaseClinicalDataDevelopmentErythrocytesFood ContaminationGeneticGoalsGranulomaGrowthHematopoieticHost DefenseHumanImmuneImmune systemImmunocompetentInductively Coupled Plasma Mass SpectrometryInfectionInflammatoryIngestionInterferon Type IIIronLeishmaniaLeukocytesLymphoid TissueMethodsMicrobeModelingMolecularMusMycobacterium lepraeMycobacterium tuberculosisPathologyPathway interactionsPhagocytesPhaseProteomicsPublic HealthRelapseSalmonellaSalmonella entericaSalmonella typhimuriumSerotypingSiteSystemSystemic infectionTestingTherapeuticTissuesToxinTyphoid Feveralpha Toxinantimicrobialbasecell typecontaminated watercytokineexperimental studyinhibitor/antagonistmacrophagemetal transporting protein 1novel therapeuticspathogenuptake
中文摘要
总结
肠道沙门氏菌亚种鼠伤寒沙门氏菌是小鼠的天然病原体,
感染沙门氏菌通常存在于专职吞噬细胞内,通常是巨噬细胞,这是至关重要的
发展成慢性感染然而,目前还不清楚沙门氏菌是如何在一种细胞类型中存活的。
它们进化到可以消灭病原体我们的实验室已经证明,在持续的小鼠感染,S。
鼠伤寒沙门氏菌可以存在于噬血细胞的巨噬细胞内。噬血细胞巨噬细胞(HM)
特征在于摄取造血谱系的活细胞,并且临床上与
人类伤寒我们还观察到,感染后三周,活化的巨噬细胞,
可能是HM囊泡,合并成肉芽肿,这些肉芽肿隐藏并似乎保护细菌免受宿主免疫
系统,可能建立一个网站,在那里细菌可以长期生存。这项提案的目的是
确定S.鼠伤寒杆菌利用巨噬细胞,包括肉芽肿内的HM和巨噬细胞,
在急性和慢性感染期间抵抗宿主防御。我们正在模拟HM肉芽肿和肉芽肿
以下两个目标将解决有关细菌如何建立和维持定植的关键问题。
HM肉芽肿和肉芽肿内的组织:1)S。鼠伤寒从巨噬细胞获得铁?和
2)S如何鼠伤寒杆菌能在肉芽肿中存活吗肉芽肿如何形成、获得和维持
诸如沙门氏菌的细菌仍然是一个知之甚少的领域,其可能能够被治疗剂靶向。
英文摘要
Summary
Salmonella enterica subspecies Typhimurium is a natural pathogen of mice that establishes persistent, systemic
infection. Salmonella generally reside within professional phagocytes, typically macrophages, which is critical
for the development of chronic infection. However, it is unclear how Salmonella can survive within a cell-type
that evolved to destroy pathogens. Our lab has demonstrated that during persistent murine infections, S.
Typhimurium can reside within macrophages that are hemophagocytic. Hemophagocytic macrophages (HMФs)
are characterized by the ingestion of viable cells of the hematopoietic lineages, and are clinically associated with
human Typhoid fever. We have also observed that by three weeks post-infection, activated macrophages, and
possibly HMФs, coalesce into granulomas that harbor and appear to protect bacteria from the host immune
system, potentially establishing a site at which the bacteria can survive long-term. The goal of this proposal is
to determine how S. Typhimurium exploits macrophages, including HMФs and macrophages within granulomas,
to withstand host defenses during acute and chronic infection. We are modeling HMФs and granulomas and the
following two aims will address key questions regarding how bacteria establish and maintain colonization of
tissues within HMФs and granulomas: 1) How does S. Typhimurium acquire iron from macrophages? and
2) How does S. Typhimurium survive in granulomas? How granulomas form and acquire and maintain
bacteria such as Salmonella remains a poorly understood area that may be able to be targeted with therapeutics.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Infection-Dependent Vulnerabilities of Gram-negative Bacterial Pathogens
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批准号:10592676
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项目类别:
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资助金额:$50.87万
-
财政年份:2023
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负责人:Corrella S Detweiler
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依托单位:
Using Salmonella Pathogenesis and Cell Biology as a Discovery Tool
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批准号:10665946
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项目类别:
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资助金额:$23.48万
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财政年份:2023
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负责人:Corrella S Detweiler
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依托单位:
A Small Molecule That Blocks Salmonella Replication in Macrophages
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批准号:10312125
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项目类别:
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资助金额:$19.25万
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财政年份:2020
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负责人:Corrella S Detweiler
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依托单位:
Chemical Probes for Bacteria-Macrophage Interactions
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批准号:9171993
-
项目类别:
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资助金额:$19.24万
-
财政年份:2016
-
负责人:Corrella S Detweiler
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依托单位:
A Novel Screen for Antibacterials that Are Non-Toxic to Mammals
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批准号:9186486
-
项目类别:
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资助金额:$22.52万
-
财政年份:2015
-
负责人:Corrella S Detweiler
-
依托单位:
A Novel Screen for Antibacterials that Are Non-Toxic to Mammals
-
批准号:9015218
-
项目类别:
-
资助金额:$18.64万
-
财政年份:2015
-
负责人:Corrella S Detweiler
-
依托单位:
Host Pathways that Enable /Salmonella/ Replication Within Hemophagocytic Macropha
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批准号:8281809
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项目类别:
-
资助金额:$22.88万
-
财政年份:2012
-
负责人:Corrella S Detweiler
-
依托单位:
Host Pathways that Enable /Salmonella/ Replication Within Hemophagocytic Macropha
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批准号:8418684
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项目类别:
-
资助金额:$19.06万
-
财政年份:2012
-
负责人:Corrella S Detweiler
-
依托单位:
Hemophagocytic Macrophages and Systemic Salmonella Infection
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批准号:8805824
-
项目类别:
-
资助金额:$37.57万
-
财政年份:2012
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负责人:Corrella S Detweiler
-
依托单位:
Hemophagocytic Macrophages and Systemic Salmonella Infection
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批准号:8433309
-
项目类别:
-
资助金额:$34.84万
-
财政年份:2012
-
负责人:Corrella S Detweiler
-
依托单位:
Hemophagocytic Macrophages and Systemic Salmonella Infection
-
批准号:8292621
-
项目类别:
-
资助金额:$18.54万
-
财政年份:2012
-
负责人:Corrella S Detweiler
-
依托单位:
Hemophagocytic Macrophages and Systemic Salmonella Infection
-
批准号:8321279
-
项目类别:
-
资助金额:$37.63万
-
财政年份:2011
-
负责人:Corrella S Detweiler
-
依托单位:
Persistent Systemic Infection of Mice by Salmonella Enterica
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批准号:7927761
-
项目类别:
-
资助金额:$17.17万
-
财政年份:2009
-
负责人:Corrella S Detweiler
-
依托单位:
Persistent Systemic Infection of Mice by Salmonella Enterica
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批准号:7628092
-
项目类别:
-
资助金额:$33.02万
-
财政年份:2007
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负责人:Corrella S Detweiler
-
依托单位:
Persistent Systemic Infection of Mice by Salmonella Enterica
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批准号:7316346
-
项目类别:
-
资助金额:$32.6万
-
财政年份:2007
-
负责人:Corrella S Detweiler
-
依托单位:
A Mammalian Cellular Niche for Chronic Bacteria
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批准号:7359240
-
项目类别:
-
资助金额:$14.79万
-
财政年份:2007
-
负责人:Corrella S Detweiler
-
依托单位:
A Mammalian Cellular Niche for Chronic Bacteria
-
批准号:7535604
-
项目类别:
-
资助金额:$18.56万
-
财政年份:2007
-
负责人:Corrella S Detweiler
-
依托单位:
Persistent Systemic Infection of Mice by Salmonella Enterica
-
批准号:7425884
-
项目类别:
-
资助金额:$33.03万
-
财政年份:2007
-
负责人:Corrella S Detweiler
-
依托单位:
Persistent Systemic Infection of Mice by Salmonella Enterica
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批准号:8077432
-
项目类别:
-
资助金额:$32.16万
-
财政年份:2007
-
负责人:Corrella S Detweiler
-
依托单位:
Persistent Systemic Infection of Mice by Salmonella Enterica
-
批准号:7876718
-
项目类别:
-
资助金额:$32.51万
-
财政年份:2007
-
负责人:Corrella S Detweiler
-
依托单位:
海外基金