**2. Inflammasomes**

The ability to activate immune cells depends on the presence of molecular multiprotein inflammasome complexes [37,38]. Inflammasomes are high molecular-weight multimeric self-assembling protein complexes of the innate immune system, which are not only important for initiating the inflammatory response and release of IL-1β and IL-18 (Figure 2), but also in regulating cellular apoptosis [38]. As shown in the schematic diagram, signaling for inflammasome activation occurs in two stages. Priming in stage 1 is followed by activation of inflammasome complex by interaction with several components. The inflammasome complex contains a sensor molecule, an adaptor protein and the pro-inflammatory caspase-1 [37,39]. Inflammasomes act as a finely tuned alarm, triggering and amplifying systems in response to cellular stresses and/or infections. Placental trophoblasts, endothelial cells and macrophages can sense and respond to a variety of infectious agents by the presence of the pattern recognition receptors (PRRs). The PRRs have the ability to sense pathogen-associated molecular patterns (PAMPs) that are expressed by microbes, as well as noninfectious (sterile inflammation) host-derived damage associated molecular patterns (DAMPs) including reactive oxygen species, uric acid, cholesterol, microparticles, and exosomes (namely alarmins) [40,41] (Figure 2). When activated, the inflammasome machinery has the potential to promote maturation and release of pro-inflammatory cytokines including the release of danger signals, as well as pyroptosis, a rapid, pro-inflammatory form of cell death [42].

**Figure 2.** Activation and formation of inflammasome complex. Two-step signaling mechanisms are involved in the formation inflammasome complexes: The first "priming" signal initiated by infectious agents such as LPS, enhances the expression of inflammasome components and target proteins via activation of transcription factor NF-κB. The second "activation" signal promotes the assembly of inflammasome components. The second signal also involves three major mechanisms, including lysosomal damage, and the potassium efflux. Nigericin is a microbial toxin that alters potassium efflux. Abbreviations: LPS: Lipopolysaccharide; TLR: Toll-like receptor; PAMPs: Pathogen-associated molecular patterns; DAMPs: Danger-associated molecular patterns; ROS: Reactive oxygen species.
