Epithelial type I interferon signaling in Salmonella typhimurium infection
鼠伤寒沙门氏菌感染中上皮 I 型干扰素信号传导
基本信息
- 批准号:9506338
- 负责人:
- 金额:$ 23.78万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-06-08 至 2020-05-31
- 项目状态:已结题
- 来源:
- 关键词:AblationAcuteAddressAnimalsBacterial InfectionsBindingCaspaseCell DeathCell NucleusComplexCytokine ReceptorsCytokine SignalingDataDefectDefense MechanismsDevelopmentEnteralEnvironmentEpithelialEpithelial CellsEquilibriumExhibitsGastroenteritisGenesGeneticGenetic TranscriptionHomoHost DefenseIFNAR1 geneImmune responseImmune systemImmunologicsInfectionInflammasomeInflammationInflammation MediatorsInflammatoryInflammatory ResponseInflammatory disease of the intestineInterferon Type IInterferon-alphaInterferonsIntestinesInvadedJanus kinaseKnowledgeMicrobeMusNeutrophil InfiltrationNitratesPathway interactionsPhosphorylationPopulationPositioning AttributeProteinsReceptor SignalingRoleSTAT proteinSTAT1 geneSTAT2 geneSalmonellaSalmonella entericaSalmonella infectionsSalmonella typhimuriumSerotypingSignal TransductionTestingUnited StatesVacuoleWild Type Mousebasecommensal microbescytokinedefense responseenteric pathogenfoodbornegut microbiotain vitro Assayinnovationintestinal epitheliummicrobial communitymicrobiotamicroorganismmutantneutrophilpathogenpublic health relevancereceptorreceptor bindingtranscription factor
项目摘要
SUMMARY
Cytokines are key mediators of inflammation and the host immune response. For many
cytokines, signaling cascades are initiated by the binding of cytokines to their cognate receptor
and the phosphorylation of Signal Transducers and Activators of Transcription (STAT) proteins by
receptor bound Janus kinases (JAK). STAT proteins then form homo or heterodimer complexes,
which translocate to the nucleus and regulate the transcription of multiple genes. Despite the high
number of cytokines, there are only seven different STAT proteins that determine the fate of
cytokine receptor signaling. Type I IFN signaling cascades begin following the binding of IFN/ to
their cognate receptor (IFNAR). IFNAR activation leads to the formation of STAT1/STAT1
homodimers and STAT1/STAT2 heterodimers that each trigger distinct signaling cascades.
Animals deficient in STAT1 signaling or IFNAR exhibit defects in inflammasome formation,
caspase activation, and inflammatory cell death during infection with S. Typhimurium. However, it
remains unclear whether genetic ablation of STAT1/STAT2 signaling alone changes the host
response to Salmonella infection. The objectives of this application are to determine the
mechanisms by which STAT2 dependent type I interferon signaling in epithelial cells contributes to
intestinal inflammation that enables S. Typhimurium to outgrow the microbiota. Our central
hypothesis that STAT2-dependent type I IFN signaling in epithelial cells leads to neutrophil
recruitment, which in turn creates a microaerophilic and nitrate-rich environment enabling the
luminal outgrowth of S. Typhimurium.
总结
细胞因子是炎症和宿主免疫应答的关键介质。对于许多
细胞因子,信号级联是由细胞因子与其同源受体的结合引发的
以及信号转导和转录激活因子(STAT)蛋白的磷酸化,
受体结合Janus激酶(JAK)。STAT蛋白然后形成同源或异源二聚体复合物,
转移到细胞核并调节多个基因的转录。尽管高
在许多细胞因子中,只有七种不同的STAT蛋白决定了细胞因子的命运。
细胞因子受体信号传导。I型IFN信号传导级联开始于IFN γ/IFN β与
其同源受体(IFNAR)。IFNAR激活导致STAT 1/STAT 1的形成
同源二聚体和STAT 1/STAT 2异源二聚体,其各自触发不同的信号传导级联。
STAT 1信号传导或IFNAR缺陷的动物表现出炎性小体形成的缺陷,
半胱天冬酶激活和炎性细胞死亡。鼠伤寒但
目前尚不清楚单独基因切除STAT 1/STAT 2信号传导是否会改变宿主
对沙门氏菌感染的反应。本申请的目的是确定
上皮细胞中STAT 2依赖性I型干扰素信号传导的机制
肠道炎症使S.使鼠伤寒杆菌的数量超过微生物的数量。我们的中央
上皮细胞中STAT 2依赖性I型IFN信号转导导致中性粒细胞
招聘,这反过来又创造了一个微需氧和硝酸盐丰富的环境,使
腔生长S.鼠伤寒
项目成果
期刊论文数量(0)
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会议论文数量(0)
专利数量(0)
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{{ truncateString('Cagla Tukel', 18)}}的其他基金
Molecular mechanisms of Salmonella mediated autoimmunity
沙门氏菌介导的自身免疫的分子机制
- 批准号:
10031214 - 财政年份:2020
- 资助金额:
$ 23.78万 - 项目类别:
Molecular mechanisms of Salmonella mediated autoimmunity
沙门氏菌介导的自身免疫的分子机制
- 批准号:
10624790 - 财政年份:2020
- 资助金额:
$ 23.78万 - 项目类别:
Molecular mechanisms of Salmonella mediated autoimmunity
沙门氏菌介导的自身免疫的分子机制
- 批准号:
10402395 - 财政年份:2020
- 资助金额:
$ 23.78万 - 项目类别:
Molecular mechanisms of Salmonella mediated autoimmunity
沙门氏菌介导的自身免疫的分子机制
- 批准号:
10834303 - 财政年份:2020
- 资助金额:
$ 23.78万 - 项目类别:
The role of bacterial amyloid curli in Alzheimer's Disease
细菌淀粉样蛋白卷曲在阿尔茨海默病中的作用
- 批准号:
10714005 - 财政年份:2020
- 资助金额:
$ 23.78万 - 项目类别:
Molecular mechanisms of Salmonella mediated autoimmunity
沙门氏菌介导的自身免疫的分子机制
- 批准号:
10159212 - 财政年份:2020
- 资助金额:
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Bacterial amyloids: interactions with DNA and pathogenicity
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9551789 - 财政年份:2017
- 资助金额:
$ 23.78万 - 项目类别:
Immune recognition of amyloid/extracellular DNA complexes
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- 批准号:
9373285 - 财政年份:2017
- 资助金额:
$ 23.78万 - 项目类别:
Inflammasome activation by Salmonella typhimurium biofilms
鼠伤寒沙门氏菌生物膜激活炎症小体
- 批准号:
9282745 - 财政年份:2016
- 资助金额:
$ 23.78万 - 项目类别:
Inflammasome activation by Salmonella typhimurium biofilms
鼠伤寒沙门氏菌生物膜激活炎症小体
- 批准号:
9167723 - 财政年份:2016
- 资助金额:
$ 23.78万 - 项目类别:
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