Studies have linked the NLRP3 inflammasome pathway to the elaboration of sterile inflammation. CD36 serves a dual role by priming transcription of the gene encoding interleukin 1ß (IL-1ß) and inducing assembly of the NLRP3 inflammasome complex, which leads to the release of active IL-1ß. emphasized the clinical importance of PRRs in noninfectious disorders, very little is known about the underlying mechanisms by which PRRs operate in this context. Among the PRRs linked to sterile inflammation, the NLRs seem to have attracted the most attention4, 5. Most members of the NLR family are unusual PRRs in that they do not function to upregulate the transcription of genes encoding inflammatory cytokines, chemokines or interferons. Rather than regulating the expression of cytokineencoding genes, many NLRs trigger secretion of cytokines of the interleukin 1 (IL-1) family. The secretion of IL-1 is achieved via the ability of NLRs to assemble cytoplasmic protein complexes called ‘inflammasomes’. The inflammasome is a protein-processing machine that uses proteases to cleave precursor (‘pro-’) forms of IL-1 in the cytosol, which are then somehow secreted to induce inflammation. Because NLRs cannot activate transcription, yet they promote the secretion of inducible cytokines, NLRs usually depend on other PRRs to induce cytokine expression. Thus, present models of infection-induced immune responses mediated by the IL-1 family propose that two signals are necessary. Signal 1 is provided by a transcription-inducing PRR (such as a TLR), which upregulates expression of members of the IL-1 family and some NLRs themselves. Signal 2 is then provided that activates the NLR to assemble an inflammasome and cause the secretion of proinflammatory members of the IL-1 family6. In an interesting turn of events, Sheedy et al. now report that the scavenger receptor CD36 can provide both signal 1 and signal 2 to promote inflammasome activation by sterile stimuli3. This finding helps explain the importance of CD36 in atherosclerosis7 and identifies a previously unknown means by which the innate immune system can be activated differently by microbes or endogenous triggers.