The innate immune system is a complex network of cells and proteins that are designed to protect your body against harmful microbes and molecules. At the forefront of this system is the inflammasome, a multiprotein complex engineered to detect danger signals and then orchestrate the immune response.
Structure of the Inflammasome
The inflammasome is a molecular machine that is composed of various components. The primary components are receptors that recognize damage-associated molecular patterns (DAMPs) which indicate cellular stress or microbe infection. The DAMPs are detected by pattern-recognition receptors (PRRs) and nod-like receptors (NLRs). After the signals have been detected PRRs oligomerize and recruit an adaptor protein called ASC. This forms an assembly that activates caspase-1 which is a key enzyme in the inflammasome cascade.
Activated Caspase-1
Activated caspase-1 is the executioner of the inflammasome pathway. It cleaves pro-inflammatory cytokines (IL-1B and IL-18) into their active forms. These cytokines are potent signaling molecules that trigger and amplify the inflammatory responses. These responses can include the recruitment of immune cells to sites of infection, or in repairing tissue damage.
The Inflammasome in Disease
In a healthy immune system the inflammasome is tightly regulated and is only turned on when needed. However due to its high potency dysfunction of the inflammasome can lead to a variety of diseases. It has been implicated in chronic inflammatory disorders, autoimmune disorders, and neurodegenerative disease. An overactive inflammasome, such as in rheumatoid arthritis, can lead to continuous inflammation and causes damage to healthy tissues and cells.
Current Focus
The understanding of regulation and molecules involved in the inflammasome is still not completely understood. Current research is focusing on the various genes and proteins that are involved in the inflammasome cascade. With increased knowledge of the regulation of this part of the immune system potential drugs and therapies for inflammatory diseases can be evaluated.
References
de Zoete, M. R., Palm, N. W., Zhu, S., & Flavell, R. A. (2014). Inflammasomes. Cold Spring Harbor Perspectives in Biology, 6(12). https://doi.org/10.1101/cshperspect.a016287
Guo, H., Callaway, J. B., & Ting, J. P-Y. (2015). Inflammasomes: mechanism of action, role in disease, and therapeutics. Nature Medicine, 21(7), 677–687. https://doi.org/10.1038/nm.3893
Ketelut-Carneiro, N., & Fitzgerald, K. A. (2020). Inflammasomes. Current Biology, 30(12), R689–R694. https://doi.org/10.1016/j.cub.2020.04.065
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