Domain-specific role of IL-17RA in controlling Klebsiella pneumoniae lung infection
Domain-specific role of IL-17RA in controlling Klebsiella pneumoniae lung infection
批准号:
10219359
负责人:
Giraldina Trevejo-Nunez
金额:
$7.83万
依托单位国家:
美国
项目类别:
财政年份:
2020
资助国家:
美国
项目状态:
已结题
起止时间:
2020-07-20 至 2023-06-30
关键词:
AccountingAddressAlveolar CellAnimal ModelBiological Response ModifiersCellsClinicalCommunitiesDiseaseDistalEndothelial CellsEpithelialEpithelial CellsEventFibroblastsGenesGenetic studyGoalsHistidineImmuneImmune responseImmunityImmunocompromised HostImmunologicsImpairmentIn VitroInfectionInfection ControlInflammationInterleukin-17Klebsiella pneumoniaeKnowledgeLaboratoriesLengthLungLung infectionsMediatingMediator of activation proteinMedicalMessenger RNAMolecularMorbidity - disease rateMulti-Drug ResistanceMusMutant Strains MiceNF-kappa BPneumoniaPositioning AttributePredispositionProcessProteinsReceptor SignalingResearchResistanceResistance profileResolutionRoleSecondary toSignal TransductionStromal CellsTestingUnited Statesbronchial epitheliumcell typecytokineexperimental studyhealthcare-associated infectionsin vivoinsightinterleukin-17Cinterleukin-17Emortalitymouse modelmutantpathogenreceptorreceptor functionresponsesingle-cell RNA sequencingtranscriptome sequencing
中文摘要
摘要
IL-17是肺炎克雷伯氏菌(Klebsiella pneumoniae,KP)免疫的重要介质。缺乏IL-17信号传导的动物模型
或具有IL-17受体(IL-17 R)缺乏的患者易患KP肺炎。虽然大量的研究
目前的研究主要集中在Th 17细胞是如何产生和调节的,IL-17及其受体的作用机制等方面。
受体IL-17 R介导相关疾病过程中的特异性下游信号,如KP肺炎,
没有完全阐明。我们在小鼠模型中了解KP肺炎的努力表明,
IL-17 RA,也称为CBAD,对于控制这种感染是必不可少的。因此,我们建议确定
IL-17 RA CBAD结构域限制KP肺炎的免疫和分子机制。我们将
还进行平行分析以通过单细胞RNASeq评估细胞类型特异性应答。这些发现
从这个建议中产生的将有助于我们理解IL-17依赖的信号传导机制,
肺炎可以得到控制,并以单细胞分辨率评估肺免疫应答。
英文摘要
ABSTRACT
IL-17 is an essential mediator of immunity to Klebsiella pneumoniae (KP). Animal models lacking IL-17 signaling
or having IL-17 receptor (IL-17R) deficiency are susceptible to KP pneumonia. Although considerable research
effort has focused on how Th17 cells are generated and regulated, the mechanisms by which IL-17 and its
receptor IL-17R mediate specific downstream signals in relevant disease processes such as KP pneumonia are
not fully elucidated. Our efforts to understand KP pneumonia in mouse models revealed that the distal domain
of IL-17RA, also known as CBAD, is indispensable to control this infection. Thus, we propose to determine the
immune and molecular mechanisms by which the IL-17RA CBAD domain constrains KP pneumonia. We will
also perform parallel analyses to evaluate the cell-type-specific response by single-cell RNASeq. The findings
generated from this proposal will help us understand IL-17- dependent signaling mechanism by which KP
pneumonia can be controlled and to evaluate the lung immune response at a single cell resolution.
期刊论文(3)
专著(0)
科研奖励(0)
会议论文
DOI:
10.1128/mbio.03792-21
发表时间:
2021-02-22
期刊:
mBio
影响因子:
6.4
作者:
[Trevejo-Nuñez G, Lin B, Fan L, Aggor FEY, Biswas PS, Chen K, Gaffen SL]
通讯作者:
Gaffen SL
DOI:
10.4049/immunohorizons.2300082
发表时间:
2024-01-01
期刊:
ImmunoHorizons
影响因子:
--
作者:
[Lin B, Fan L, Jackson S, Matunis AR, Lou D, Chen K, Trevejo-Nuñez G]
通讯作者:
Trevejo-Nuñez G
Negative regulation of inflammation during Klebsiella pneumoniae infection
-
批准号:10404122
-
项目类别:
-
资助金额:$19.82万
-
财政年份:2021
-
负责人:Giraldina Trevejo-Nunez
-
依托单位:
Negative regulation of inflammation during Klebsiella pneumoniae infection
-
批准号:10301091
-
项目类别:
-
资助金额:$23.48万
-
财政年份:2021
-
负责人:Giraldina Trevejo-Nunez
-
依托单位:
Domain-specific role of IL-17RA in controlling Klebsiella pneumoniae lung infection
-
批准号:10063356
-
项目类别:
-
资助金额:$7.83万
-
财政年份:2020
-
负责人:Giraldina Trevejo-Nunez
-
依托单位:
Role of IL-22/IL-22RA2 during pneumococcal pneumonia
-
批准号:10198015
-
项目类别:
-
资助金额:$16.73万
-
财政年份:2017
-
负责人:Giraldina Trevejo-Nunez
-
依托单位:
Role of IL-22/IL-22RA2 during pneumococcal pneumonia
-
批准号:9978108
-
项目类别:
-
资助金额:$16.73万
-
财政年份:2017
-
负责人:Giraldina Trevejo-Nunez
-
依托单位:
海外基金