Bacterial modulation of noncanonical inflammasome
非典型炎症小体的细菌调节
基本信息
- 批准号:9520701
- 负责人:
- 金额:$ 39.88万
- 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:2018-01-16 至 2022-12-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAddressAffectAnimal ModelAnti-Bacterial AgentsAntibioticsAutophagocytosisBacteriaBacterial InfectionsBindingCASP1 geneCaspaseCell DeathCell Death InductionChildCitrobacter rodentiumCytosolDetectionDevelopmentEndosomesEscherichia coliEscherichia coli EHECEscherichia coli InfectionsEscherichia coli K12GenesGenetic EngineeringGenomic IslandsGram-Negative BacteriaGram-Negative Bacterial InfectionsHemolytic-Uremic SyndromeHemorrhagic colitisHospitalizationHost DefenseHumanImmuneImmune signalingImmunologic SurveillanceInfectionInfectious AgentInflammasomeInflammatoryInnate Immune ResponseInnate Immune SystemInterleukin-1Interleukin-1 betaInterleukin-18Interleukin-6InvadedIslandKnowledgeLibrariesLifeLysosomesMediatingMembraneMitomycinsMobile Genetic ElementsMultiprotein ComplexesMusNatural ImmunityNatureOutcomePathway interactionsPattern recognition receptorPlayProductionProteinsRegulationResistanceRoleSeverity of illnessShiga ToxinSignal PathwaySignal TransductionSurveysSystemTNF geneToxic effectTranslationsUnited StatesVesicleVirulenceVirulence Factorsantimicrobialarmbasechemical geneticscytokinedefense responsedesignenteric pathogengenetic elementimmunomodulatory drugsin vivoinducible gene expressioninsightmacrophagemicrobialmutantnovelnovel therapeutic interventionnovel therapeuticspathogenpathogenic bacteriapressureresponsescreeningtherapeutic vaccinetrafficking
项目摘要
Project Summary/Abstract
The innate immune system employs germline-encoded pattern recognition receptors to
survey the extra- and intra-cellular milieu for the presence of invading microbial or danger
signals and mount appropriate defense responses. Inflammasomes, the multiprotein complexes
assembled in the cytosol in response to microbial and endogenous danger signals, have
emerged as a central component of the innate immune surveillance system. Once assembled
inflammasomes proteolytically activate caspase-1, which in turn induces cell death and
production of IL-1β and IL-18. Most recently a noncanonical NLRP3 inflammasome pathway
was identified that is activated by LPS that enters the cytosol via outer membrane vesicles
during infection with Gram-negative bacteria such as Enterohemorrhagic E. coli (EHEC).
Cytosolic LPS binds and activates an inflammatory caspase, caspae-11, which then mediates
cell death, caspase-1 activation and downstream IL-1 cytokine production. Inflammasomes,
including the caspase-11-mediated noncanonical inflammasome, play a crucial role in the
clearance of infectious agents via pyroptotic and IL-1 responses. A strong selection pressure
from the host such as this drives pathogens to develop strategies to actively antagonize or
evade innate immune responses. However, little is known about regulation of caspase-11-
mediated noncanonical inflammasome by bacterial pathogens. This project will address
this knowledge gap and will focus on examining the modulation of noncanonical inflammasome
by bacteria utilizing EHEC as a model organism. The studies proposed in the three specific
aims of this project will systematically characterize how two bacterial virulence factors inhibit the
noncanonical inflammasome and determine the underlying mechanisms. Identifying the
mechanisms by which pathogenic bacteria silence noncanonical inflammasome is crucial as it
may aid in designing novel therapeutic approaches against Gram-negative infections.
项目总结/文摘
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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Sivapriya Kailasan Vanaja其他文献
Sivapriya Kailasan Vanaja的其他文献
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{{ truncateString('Sivapriya Kailasan Vanaja', 18)}}的其他基金
Outer Membrane Vesicles in Shiga Toxin-Mediated Inflammatory and Thrombotic Responses Leading to Systemic Disease
志贺毒素介导的导致全身性疾病的炎症和血栓反应中的外膜囊泡
- 批准号:
10668016 - 财政年份:2023
- 资助金额:
$ 39.88万 - 项目类别:
Bacterial modulation of noncanonical inflammasome
非典型炎症小体的细菌调节
- 批准号:
10311512 - 财政年份:2018
- 资助金额:
$ 39.88万 - 项目类别:
Bacterial modulation of noncanonical inflammasome
非典型炎症小体的细菌调节
- 批准号:
10893667 - 财政年份:2018
- 资助金额:
$ 39.88万 - 项目类别:
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