Resetting the Body's Danger Sensor

The human body has a sophisticated danger-sensing mechanism that alerts the immune system when something is not right. This molecular sensor is called the inflammasome — a complex structure consisting of multiple proteins that send out chemical flares that trigger the immune system and protect sensitive tissues. Inflammasomes protect us from the constant barrage of environmental threats and invading pathogens. However, in the case of chronic diseases, the inflammasome’s warning signals get stuck in an on position, a dysfunctional state with devastating effects on human health.

Inflammasomes are receptors that are part of the innate immune system and work by regulating the activation of an enzyme called caspase-1. Once activated, caspase-1 initiates a flood of proinflammatory cytokines to the site, calling phagocytic immune cells such as macrophages to the scene to gobble up microbes and cellular debris to allow for healing and tissue restoration to begin.

While most of the danger sensors in the body are sensitive to bacteria and viruses, some respond to physiological changes in human cells: the formation of crystals, protein aggregates, and signs of damaged or stressed cells, for example. A growing body of evidence is pointing to just how important the inflammasome is in the development of conditions such as Alzheimer’s disease, cancer, and osteoarthritis, and how therapeutic strategies to turn off these proinflammatory signals may help patients find relief. 

In Alzheimer’s disease, the formation of amyloid plaques in brain tissues can set off inflammasomes in the brain, creating a constant state of inflammation that can exacerbate neural tissue damage and accelerate the patient’s cognitive decline. This vicious cycle is also observed in cancerous tissues, where tumor cells trigger the inflammasome, only to create an inflammatory microenvironment that allows tumors to grow and thrive.

Clinical strategies to block the signals that the inflammasome emits are now a major drug development focus for biopharma. Companies such as IFM Therapeutics specialize in creating ways of targeting and modulating the innate immune system when it is overactive in disease states such as autoimmune disorders and cancer. Inflammasome therapies are currently in early-stage clinical trials, with many more in the pipeline to treat an array of chronic diseases.

Sources: Nature, Novartis, Molecular Cancer.