The NLRP3 inflammasome activation in human or mouse cells, sensitivity causes puzzle

According to our current understanding, the NLR family, pyrin domain containing 3 (NLRP3) infl ammasome activation is generally a two-step process.The fi rst step is priming, in which pathogen associated molecular patterns (PAMPs) such as LPS or pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) induced NF-κB activation provides synthesis of pro-IL-1β and NLRP3 proteins.This priming step is considered as signal 1, which makes the cell ready for a second strike to assemble the infl ammasome.Then danger signals such as ATP and MSU provide the signal 2 that promotes formation of the NLRP3 infl ammasome and activates caspase-1.Both of these 2 steps are required in mouse macrophages for the NLRP3 inflammasome activation (Dinarello, 2007).However, in human monocytes and macrophages, PAMPs such as LPS alone can lead to secretion of mature IL-1β without a second signal (Netea et al., 2009;Shenoy et al., 2012).It seems that in human cells signal 1 alone is enough to activate the NLRP3 inflammasome.The reason for this difference may attribute to constitutive caspase-1 activation in primary monocytes in some cases (Netea et al., 2009).Presumably