Document Detail


Elevated AIM2-mediated pyroptosis triggered by hypercytotoxic Francisella mutant strains is attributed to increased intracellular bacteriolysis.
MedLine Citation:
PMID:  21883803     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Intracellular bacterial pathogens Francisella novicida and the Live Vaccine Strain (LVS) are recognized in the macrophage cytosol by the AIM2 inflammasome, which leads to the activation of caspase-1 and the processing and secretion of active IL-1β, IL-18 and pyroptosis. Previous studies have reported that F. novicida and LVS mutants in specific genes (e.g. FTT0584, mviN and ripA) induce elevated inflammasome activation and hypercytotoxicity in host cells, leading to the proposal that F. novicida and LVS may have proteins that actively modulate inflammasome activation. However, there has been no direct evidence of such inflammasome evasion mechanisms. Here, we demonstrate for the first time that the above mutants, along with a wide range of F. novicida hypercytotoxic mutants that are deficient for membrane-associated proteins (ΔFTT0584, ΔmviN, ΔripA, ΔfopA and ΔFTN1217) or deficient for genes involved in O-antigen or LPS biosynthesis (ΔwbtA and ΔlpxH) lyse more intracellularly, thus activating increased levels of AIM2-dependent pyroptosis and other innate immune signalling pathways. This suggests that an inflammasome-specific evasion mechanism may not be present in F. novicida and LVS. Furthermore, future studies may need to consider increased bacterial lysis as a possible cause of elevated stimulation of multiple innate immune pathways when the protein composition or surface carbohydrates of the bacterial membrane is altered.
Authors:
Kaitian Peng; Petr Broz; Jonathan Jones; Lydia-Marie Joubert; Denise Monack
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-08-24
Journal Detail:
Title:  Cellular microbiology     Volume:  13     ISSN:  1462-5822     ISO Abbreviation:  Cell. Microbiol.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-09-14     Completed Date:  2012-01-06     Revised Date:  2014-09-15    
Medline Journal Info:
Nlm Unique ID:  100883691     Medline TA:  Cell Microbiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1586-600     Citation Subset:  IM    
Copyright Information:
© 2011 Blackwell Publishing Ltd.
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MeSH Terms
Descriptor/Qualifier:
Bacteriolysis*
Caspase 1 / metabolism
Cell Death*
Francisella / immunology*,  pathogenicity*
Inflammasomes / metabolism
Macrophages / immunology*,  microbiology*
Nuclear Proteins / metabolism*
Grant Support
ID/Acronym/Agency:
AI063302/AI/NIAID NIH HHS; AI065359/AI/NIAID NIH HHS; P01 AI063302/AI/NIAID NIH HHS; P01 AI063302-09/AI/NIAID NIH HHS; T32 AI007328/AI/NIAID NIH HHS; U54 AI065359/AI/NIAID NIH HHS; U54 AI065359-08/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/AIM2 protein, human; 0/Inflammasomes; 0/Nuclear Proteins; EC 3.4.22.36/Caspase 1
Comments/Corrections

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