Dendritic cell KLF2/Notch Axis and Th2 Responses to Eukaryotic Pathogens
树突状细胞 KLF2/Notch 轴和 Th2 对真核病原体的反应
基本信息
- 批准号:9195249
- 负责人:
- 金额:$ 51.27万
- 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
- 起止时间:2016-06-10 至 2021-05-31
- 项目状态:已结题
- 来源:
- 关键词:AmericasBacterial InfectionsBiologicalBreathingCD4 Positive T LymphocytesCell DeathCell Differentiation processCell ProliferationCell physiologyCellsCessation of lifeChemotactic FactorsCommunicationComplementDataDefectDendritic CellsDevelopmentDiseaseEmbryonic DevelopmentEquilibriumEukaryotaEvolutionFamilyGenesGenomicsHealthHelminthsHelper-Inducer T-LymphocyteHistoplasma capsulatumHost resistanceHumanHypoxiaITGAX geneImmune responseImmune systemImmunityIndiumInfectionInfection ControlInterleukin-13Interleukin-4InvestigationKnowledgeKruppel-like transcription factorsLeadLeishmaniaLicensingLigandsLungMediator of activation proteinMicrobeMolecular TargetMorbidity - disease rateMorphogenesisMusMyeloid CellsNatural ImmunityNitric OxidePathway interactionsPhenotypePopulationProcessProductionPropertyRegulationResistance to infectionResolutionRoleSeveritiesShapesSignal TransductionT-Cell ActivationT-LymphocyteTestingTh1 CellsUp-RegulationVacuumWorkadaptive immunityantimicrobialchromatin immunoprecipitationcytokineequilibration disorderextracellularfungusin vivoinsightlymph nodesmacrophagemonocytemortalitynotch proteinnovel therapeuticspathogenreceptorresponsetranscription factortranscriptome sequencing
项目摘要
Infection with eukaryotic pathogens places an enormous burden on the health of many species including
humans. Intracellular eukaryotic pathogens such as the dimorphic fungus, Histoplasma capsulatum (Hc), require
a T helper (Th) 1 response to promote elimination. Th2 that produce interleukin (IL)-4 and IL-13 override the
influence of Th1 and exaggerate the severity of infection to this fungus. While a Th2 response is detrimental to
Hc and other intracellular pathogens, it is vital for clearance of helminths. Activation of Th1 or Th2 requires
communication with dendritic cells (DCs). Knowledge regarding transcriptional regulators that license the latter
to promote a Th1 or Th2 response is incomplete. We have discovered that the transcription factor, Krüppel-like
factor (KLF) 2, in DCs calibrates the vigor of the Th2 response. A loss of KLF2 in DCs enhances release of IL-4
and IL-13 by Th2 and promotes accrual of these cells in lungs of Hc-infected mice. The net result is impaired
clearance of the fungus. The enhanced release of type 2 cytokines is dependent on an expansion of DCs that
express the Notch ligand, Jagged2. These preliminary data stimulated the central hypothesis that KLF2 is a key
element in DCs that limits the magnitude of Th2 responses and thus, differentially regulates the severity of
infection with Hc or with helminths. To test this hypothesis, we propose three Specific Aims. Aim 1 will elucidate
how KLF2-deficient DCs promote Th2 immunity. Studies will examine: 1) the influence of KLF2 on conventional
DCs in lungs and draining lymph nodes, 2) the impact on Th2 recruitment, survival, and/or proliferation and 3)
the role of DC KLF2 in controlling infection with a helminth. Specific Aim 2 will shift the focus to T cells and
examine the role of Notch receptors and Notch ligands on T cell function in Hc and helminth infection. Specific
Aim 3 will explore the genomic landscape regulated by KLF2 with a focus on the transcription factor hypoxia
inducing factor-1. In addition, we will open the aperture and perform RNA-seq and chromatin
immunoprecipitation (ChIP)-Seq to identify the KLF2-dependent gene networks in DCs that regulate Notch
signaling and Th2 accrual. A better understanding of the regulation of DCs by KLF2 during infection with
intracellular and extracellular pathogens protective could lead to the development of new therapies that govern
immunity to Hc and to helminths.
真核病原体的感染给许多物种的健康造成了巨大的负担,包括
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 }}
GEORGE S. DEEPE其他文献
GEORGE S. DEEPE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('GEORGE S. DEEPE', 18)}}的其他基金
Immunopathogenesis of Histoplasmosis and TNF
组织胞浆菌病和 TNF 的免疫发病机制
- 批准号:
10377422 - 财政年份:2021
- 资助金额:
$ 51.27万 - 项目类别:
Immunopathogenesis of Histoplasmosis and TNF
组织胞浆菌病和 TNF 的免疫发病机制
- 批准号:
10227274 - 财政年份:2021
- 资助金额:
$ 51.27万 - 项目类别:
HIF Regulation of Histoplasma Pathogenesis
HIF 对组织胞浆菌发病机制的调节
- 批准号:
10327291 - 财政年份:2018
- 资助金额:
$ 51.27万 - 项目类别:
HIF Regulation of Histoplasma Pathogenesis
HIF 对组织胞浆菌发病机制的调节
- 批准号:
10084261 - 财政年份:2018
- 资助金额:
$ 51.27万 - 项目类别:
Dendritic cell KLF2/Notch Axis and Th2 Responses to Eukaryotic Pathogens
树突状细胞 KLF2/Notch 轴和 Th2 对真核病原体的反应
- 批准号:
9293248 - 财政年份:2016
- 资助金额:
$ 51.27万 - 项目类别:
GM-CSF-Induced Metal Sequestration and Histoplasma
GM-CSF 诱导的金属螯合和组织胞浆菌
- 批准号:
10437747 - 财政年份:2013
- 资助金额:
$ 51.27万 - 项目类别:
GM-CSF-Induced Metal Sequestration and Histoplasma
GM-CSF 诱导的金属螯合和组织胞浆菌
- 批准号:
9042231 - 财政年份:2013
- 资助金额:
$ 51.27万 - 项目类别:
GM-CSF-Induced Metal Sequestration and Histoplasma
GM-CSF 诱导的金属螯合和组织胞浆菌
- 批准号:
9256435 - 财政年份:2013
- 资助金额:
$ 51.27万 - 项目类别:
GM-CSF-Induced Metal Sequestration and Histoplasma
GM-CSF 诱导的金属螯合和组织胞浆菌
- 批准号:
8598633 - 财政年份:2013
- 资助金额:
$ 51.27万 - 项目类别:
GM-CSF-Induced Metal Sequestration and Histoplasma
GM-CSF 诱导的金属螯合和组织胞浆菌
- 批准号:
10189487 - 财政年份:2013
- 资助金额:
$ 51.27万 - 项目类别:
相似海外基金
New roles of IFN-inducible OAS proteins in innate immune defense against bacterial infections
IFN诱导的OAS蛋白在针对细菌感染的先天免疫防御中的新作用
- 批准号:
10649771 - 财政年份:2023
- 资助金额:
$ 51.27万 - 项目类别:
Derivation and validation of a clinical prediction rule to identify febrile infants 61 to 90 days old at low and non-negligible risk of invasive bacterial infections
推导和验证临床预测规则,以识别 61 至 90 天大的发热婴儿,其侵袭性细菌感染的风险较低且不可忽略
- 批准号:
10574286 - 财政年份:2023
- 资助金额:
$ 51.27万 - 项目类别:
Structural and functional studies of YbtPQ for fighting bacterial infections
YbtPQ 对抗细菌感染的结构和功能研究
- 批准号:
10644889 - 财政年份:2023
- 资助金额:
$ 51.27万 - 项目类别:
A gut feeling: How can gastrointestinal bacterial infections alter female reproductive tract immunity and control of sexually transmitted infections
直觉:胃肠道细菌感染如何改变女性生殖道免疫力和性传播感染的控制
- 批准号:
MR/X031993/1 - 财政年份:2023
- 资助金额:
$ 51.27万 - 项目类别:
Research Grant
Molecular probes to diagnose pathoadapatations in bacterial infections
诊断细菌感染病理适应的分子探针
- 批准号:
EP/X014479/1 - 财政年份:2023
- 资助金额:
$ 51.27万 - 项目类别:
Research Grant
Using Small Area Variation Analysis to Investigate Sources of Practice Variation for Febrile Infants at Risk for Invasive Bacterial Infections
使用小面积变异分析来调查有侵袭性细菌感染风险的发热婴儿的实践变异来源
- 批准号:
10588846 - 财政年份:2023
- 资助金额:
$ 51.27万 - 项目类别:
Host Directed Orynotide for MDR Gram Negative Bacterial Infections
宿主定向 Orynotide 用于治疗耐多药革兰氏阴性细菌感染
- 批准号:
10674221 - 财政年份:2023
- 资助金额:
$ 51.27万 - 项目类别:
SimCell vaccines against Staphylococcus aureus bacterial infections
针对金黄色葡萄球菌细菌感染的 SimCell 疫苗
- 批准号:
10073241 - 财政年份:2023
- 资助金额:
$ 51.27万 - 项目类别:
Grant for R&D
I-Corps: Mitigating Multidrug Resistant Bacterial Infections with Biocompatible and Environmentally Benign Nanoantibiotics
I-Corps:利用生物相容性且对环境无害的纳米抗生素减轻多重耐药细菌感染
- 批准号:
2306943 - 财政年份:2023
- 资助金额:
$ 51.27万 - 项目类别:
Standard Grant
Multidimensional development of high-affinity anti-glycan antibodies to fight deadly bacterial infections
多维开发高亲和力抗聚糖抗体以对抗致命细菌感染
- 批准号:
10549640 - 财政年份:2023
- 资助金额:
$ 51.27万 - 项目类别: