Caspase-11: arming the guards against bacterial infection

As a front line of defense against pathogenic microbes, our body employs a primitive, yet highly sophisticated and potent innate immune response pathway collectively referred to as the inflammasome. Innate immune cells, epithelial cells, and many other cell types are capable of detecting infection or tissue injury and mounting a coordinated molecular defense. For example, Gram-negative bacteria are specifically detected via a surveillance mechanism that involves activation of extracellular receptors such as Toll-like receptors (TLRs) followed by intracellular recognition and activation of pathways such as caspase-11 (caspase-4/5 in humans). Importantly, lipopolysaccharide (LPS), the major component of the outer membrane of Gram-negative bacteria, is a strong trigger of these pathways. Extracellular LPS primarily stimulates TLR4, which can serve as a priming signal for expression of inflammasome components. Intracellular LPS can then trigger caspase-11-dependent inflammasome activation in the cytoplasm. Here, we briefly review the burgeoning caspase-11-dependent non-canonical inflammasome field, focusing mainly on the innate sensing of LPS.