Acute lipopolysaccharide priming boosts inflammasome activation independently of inflammasome sensor induction

Kate Schroder; Vitaliya Sagulenko; Alina Zamoshnikova; Ayanthi A Richards; Jasmyn A Cridland; Katharine M Irvine; Katryn J Stacey; Matthew J Sweet

doi:10.1016/j.imbio.2012.07.020

Acute lipopolysaccharide priming boosts inflammasome activation independently of inflammasome sensor induction

Immunobiology. 2012 Dec;217(12):1325-9. doi: 10.1016/j.imbio.2012.07.020. Epub 2012 Jul 27.

Authors

Kate Schroder¹, Vitaliya Sagulenko, Alina Zamoshnikova, Ayanthi A Richards, Jasmyn A Cridland, Katharine M Irvine, Katryn J Stacey, Matthew J Sweet

Affiliation

¹ Institute for Molecular Bioscience, University of Queensland, St Lucia 4072, Australia. K.Schroder@imb.uq.edu.au

PMID: 22898390
DOI: 10.1016/j.imbio.2012.07.020

Abstract

Macrophage pre-treatment with bacterial lipopolysaccharide (LPS) boosts subsequent activation of the NLRP3 inflammasome, which controls caspase-1-dependent pro-inflammatory cytokine maturation. Previous work has attributed this phenomenon (known as LPS 'priming') to LPS-dependent induction of NLRP3 expression. Whilst this plays a role, here we demonstrate that rapid LPS priming of NLRP3 inflammasome activation can occur independently of NLRP3 induction, since the priming effect of LPS is still apparent at short pre-treatment times in which NLRP3 protein expression remains unchanged. Furthermore, rapid LPS priming is still evident in Nlrp3(-/-) primary macrophages with NLRP3 expression reconstituted using a constitutive promoter. Similarly, we found that LPS potentiates AIM2 inflammasome activation to submaximal doses of cytosolic DNA without concomitant upregulation of AIM2 protein expression. Our data suggest that, in addition to augmenting NLRP3 inflammasome activity via NLRP3 induction, LPS boosts caspase-1 activation by the NLRP3 and AIM2 inflammasomes by an acute mechanism that is independent of inflammasome sensor induction.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Carrier Proteins / agonists
Carrier Proteins / genetics*
Carrier Proteins / immunology
Carrier Proteins / metabolism
Caspase 1 / genetics
Caspase 1 / immunology
Caspase 1 / metabolism
Cells, Cultured
Cytokines / genetics
Cytokines / immunology
Cytokines / metabolism
DNA / genetics
DNA-Binding Proteins
Humans
Inflammasomes / genetics
Inflammasomes / immunology*
Inflammasomes / metabolism
Lipopolysaccharides / immunology*
Lipopolysaccharides / pharmacology
Macrophages / immunology*
Macrophages / metabolism
Mice
NLR Family, Pyrin Domain-Containing 3 Protein
Nuclear Proteins / genetics
Nuclear Proteins / immunology
Nuclear Proteins / metabolism
Promoter Regions, Genetic / genetics
Promoter Regions, Genetic / immunology
RNA, Messenger / genetics
RNA, Messenger / immunology
Signal Transduction / genetics
Signal Transduction / immunology
Up-Regulation / genetics
Up-Regulation / immunology

Substances

AIM2 protein, human
Aim2 protein, mouse
Carrier Proteins
Cytokines
DNA-Binding Proteins
Inflammasomes
Lipopolysaccharides
NLR Family, Pyrin Domain-Containing 3 Protein
NLRP3 protein, human
Nlrp3 protein, mouse
Nuclear Proteins
RNA, Messenger
DNA
Caspase 1