Bacterial modulation of noncanonical inflammasome

非典型炎症小体的细菌调节

基本信息

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

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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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