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Elevated AIM2-mediated pyroptosis triggered by hypercytotoxic Francisella mutant strains is attributed to increased intracellular bacteriolysis

Peng, Kaitian and Broz, Petr and Jones, Jonathan and Joubert, Lydia-Marie and Monack, Denise. (2011) Elevated AIM2-mediated pyroptosis triggered by hypercytotoxic Francisella mutant strains is attributed to increased intracellular bacteriolysis. Cellular Microbiology, 13 (10). pp. 1586-1600.

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Official URL: http://edoc.unibas.ch/48482/

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Abstract

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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Infection Biology
UniBasel Contributors:Broz, Petr
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Blackwell
ISSN:1462-5814
e-ISSN:1462-5822
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:30 Nov 2017 09:34
Deposited On:30 Nov 2017 09:34

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