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Review
. 2010 Mar;40(3):620-3.
doi: 10.1002/eji.200940185.

Critical functions of priming and lysosomal damage for NLRP3 activation

Veit Hornung  1 , Eicke Latz
Affiliations
Review

Critical functions of priming and lysosomal damage for NLRP3 activation

Veit Hornung et al. Eur J Immunol. 2010 Mar.

Abstract

Inflammasomes are cytosolic multi-protein complexes that form in response to infectious or injurious challenges. Inflammasomes control the activity of caspase-1, which is essential for the maturation and release of IL-1beta family cytokines. The NLRP1, IPAF and AIM2 inflammasomes recognize specific substances, while the NLRP3 inflammasome responds to many structurally and chemically diverse triggers. Here, we discuss the critical roles of priming and lysosomal damage in NLRP3 inflammasome activation.

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Figures

Figure 1
Figure 1. Priming of the NLRP3 inflammasome
Activation of cells via the activity of TLRs, cytokine receptors, or pattern recognition receptors leads to the expression of the cytokines including the proforms of the IL-1b cytokines family. In addition NLRP3 and potentially other factors that are important for full NLRP3 activation are transcritionally induced leading to enhanced protein levels of NLRP3. A second stimulus for NLRP3 activation would then be sufficient to induce NLRP3 inflammasome activation leading to the activation of caspase-1 with subsequent cleavage of IL-1n family cytokines.
Figure 2
Figure 2. Possible mechanisms of NLRP3 inflammasome activation
Reactive oxygen species (ROS) could act on an inhibitor of NLRP3, which upon oxidation could release NLRP3 leading to its activation (I). ROS could generate an oxidized protein that would act as a ligand for NLRP3 (II). Analogously, lysosomal cathepsins could act on an inhibitory protein of NLRP3. The degradation of the putative inhibitor could lead to the release of NLRP3 and subsequent activation (III). Another possibility would be that cathepsins cleave a substrate in the cytosol, which would generate a ligand for NRLP3 (III). It is also possible that any combination of these events could be required for NLRP3 activation (V).
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