Transcriptomics

Dataset Information

6

Type I interferon signaling is required for activation of the inflammasome during Francisella infection


ABSTRACT: Francisella are pathogenic bacteria whose virulence is linked to their ability to replicate within the host cell cytosol. Entry into the macrophage cytosol activates a host protective multimolecular complex called the inflammasome to release the proinflammatory cytokines IL-1 and IL-18 and trigger caspase-1 dependent cell death. Here we show that cytosolic Francisella induce a type I interferon (IFN) response that is essential for caspase-1 activation, inflammasome mediated cell death, and release of IL-1 and IL-18. Extensive type I IFN dependent cell death resulting in macrophage depletion occurs in vivo during Francisella infection. Type I IFN is also necessary for inflammasome activation in response to cytosolic Listeria but not vacuole localized Salmonella or extracellular ATP. These results show the specific connection between type I IFN signaling and inflammasome activation, two sequential events triggered by recognition of cytosolic bacteria. To our knowledge, this is the first example of positive regulation of inflammasome activation. This connection underscores the importance of cytosolic recognition of pathogens and highlights how multiple innate immunity pathways interact before commitment to critical host responses. Keywords: murine macrophage response to Francisella tularensis subspecies novicida infection We analyzed a series of 18 MEEBO arrays on which were hybed RNA randomly amplified from bone marrow derived macrophages infected or not with WT Francisella tularensis subspecies novicida or a the mglA mutant strain GB2.

ORGANISM(S): Mus musculus  

SUBMITTER: Anna Brotcke  Thomas Henry  Lucinda J Thompson  David S Weiss  Sajeev Batra  Denise M Monack 

PROVIDER: E-GEOD-7684 | ArrayExpress | 2007-05-23

SECONDARY ACCESSION(S): GSE7684PRJNA99435

REPOSITORIES: GEO, ArrayExpress

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Publications

Type I interferon signaling is required for activation of the inflammasome during Francisella infection.

Henry Thomas T   Brotcke Anna A   Weiss David S DS   Thompson Lucinda J LJ   Monack Denise M DM  

The Journal of experimental medicine 20070423 5


Francisella tularensis is a pathogenic bacterium whose virulence is linked to its ability to replicate within the host cell cytosol. Entry into the macrophage cytosol activates a host-protective multimolecular complex called the inflammasome to release the proinflammatory cytokines interleukin (IL)-1beta and -18 and trigger caspase-1-dependent cell death. In this study, we show that cytosolic F. tularensis subspecies novicida (F. novicida) induces a type I interferon (IFN) response that is essen  ...[more]

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