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Luigi Franchi, Tatjana Eigenbrod, Gabriel Núñez, Cutting Edge: TNF-α Mediates Sensitization to ATP and Silica via the NLRP3 Inflammasome in the Absence of Microbial Stimulation, The Journal of Immunology, Volume 183, Issue 2, July 2009, Pages 792–796, https://doi.org/10.4049/jimmunol.0900173
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Abstract
The Nlrp3 inflammasome is critical for the activation of caspase-1 in response to danger signals and particulate matter. However, its role in sterile inflammation remains unclear because prestimulation of phagocytic cells with microbial molecules is required for caspase-1 activation. We show here that exposure of macrophages and dendritic cells to TNF-α promotes ATP- or silica-mediated caspase-1 activation and IL-1β secretion in the absence of microbial stimulation. The effect of TNF-α was abolished in macrophages deficient in TNF receptor I and II, Nlrp3, or ASC, whereas that induced by TLR ligands required MyD88/Trif. In addition to TNF-α, IL-1α and IL-1β promoted caspase-1 activation via Nlrp3 in response to ATP. Remarkably, macrophages tolerized to TNF-α, but not to LPS, retained full sensitivity to ATP stimulation via Nlrp3. These results provide a mechanism by which danger signals and particulate matter mediate inflammation via the Nlrp3 inflammasome in the absence of microbial infection.
