Fig. 1.

Danger signals and host defense mechanisms. Danger signals are detected via pattern recognition receptors (PRRs) to prepare defensive responses. PRRs can be classified into two main groups, membrane associated and cytosolic. NOD-like receptors (NLRs) are cytosolic PRRs, and can detect diverse ligands including ATP, fatty acids and amyloid β. NLRP3, one of the best characterized NLRs, forms large multiprotein complexes termed inflammasomes. However, the mechanism by which the NLRP3 inflammasome detects such diverse ligands is unclear. Shown in this figure is the pathway for regulation of IL-1β. Danger signals such as PAMPs are detected by TLRs and induce the synthesis of pro-IL-1β. Pro-IL-1β is processed by the oligomerized NLRP3 complex leading to secretion of IL-1β. Although psychological stress is known to increase plasma levels of IL-1β, the mechanism by which psychological stress is detected by the innate immune system is not known. Abbreviations: AIM, absent in melanoma; DAI, DNA-dependent activator of interferon (IFN)-regulatory factors; IPAF, ICE-protease activating factor; NLRP, NLR family, pyrin domain-containing; NOD, nucleotide-binding oligomerization domain.