How are inflammasomes activated?
Inflammasome activation is initiated by different kinds of cytosolic pattern recognition receptors (PRRs) that respond to either microbe-derived pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs) generated by the host cell.
What are the different types of inflammasomes?
Four key inflammasomes, namely NLRP1, NLRP3, NLRC4, and AIM2, have been best characterized. Activation of these inflammasomes leads to the processing and secretion of inflammatory cytokines, including IL-1β and IL-18, as well as leading to an inflammatory form of cell death termed pyroptosis.
What is the function of inflammasomes?
The inflammasomes are innate immune system receptors and sensors that regulate the activation of caspase-1 and induce inflammation in response to infectious microbes and molecules derived from host proteins. They have been implicated in a host of inflammatory disorders.
What are the 3 main components of an inflammasome?
An inflammasome complex comprises a sensor, an adaptor, and a zymogen procaspase-1. The functional output of inflammasome activation includes secretion of cytokines, IL-1β and IL-18, and induction of an inflammatory form of cell death called pyroptosis.
How are inflammasomes produced?
Inflammasome formation is triggered by a range of substances that emerge during infections, tissue damage or metabolic imbalances. Once the protein complexes have formed, the inflammasomes activate caspase 1, which proteolytically activates the pro-inflammatory cytokines interleukin-1β (IL-1β)3 and IL-18.
What are inflammasomes made of?
Most inflammasomes are formed with one or two NLR family members, and NLRC4 requires interaction with an NLR member of the NAIP subfamily of proteins6,14 (Figures 1 and 2A). However, non-NLR proteins such as AIM2 (Figure 2B) and pyrin can also form inflammasomes.
Where are inflammasomes found?
Inflammasomes are expressed primarily by myeloid cells and are located within the cell. The macromolecular inflammasome structure can be visualized by cryo-electron microscopy. This complex has been found to play a role in a variety of disease models in mice and several have been genetically linked to human diseases.
What are the key components and function of inflammasomes How are inflammasomes activated?
Inflammasomes are intracellular protein complexes that detect and respond to PAMPs by promoting maturation of proinflammatory IL-1β and IL-18. They can be activated directly by intracellular PAMPs or following PRR signaling (Figure 2).
What is inflammasome activation?
Inflammasome activation is initiated by different kinds of cytosolic pattern recognition receptors (PRRs) that respond to either microbe-derived pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs) generated by the host cell.
What are the receptors that activate the inflammasome complex?
These may either be on the membrane surface e.g. Toll-like receptors (TLRs) and C-type lectin receptors (CLRs) or inside the cytoplasm e.g. Nod-like receptors (NLRs) and RIG-I-like receptors (RLRs). Inflammasome complexes are activated by a subset of cytosolic PRRs that recognize a variety of microbe-derived PAMPs…
How does the inflammasome activate caspase-1?
Once active, the inflammasome binds to pro-caspase-1 (the precursor molecule of caspase-1 ), either homotypically via its own caspase activation and recruitment domain (CARD) or via the CARD of the adaptor protein ASC which it binds to during inflammasome formation.
How is the noncanonical inflammasome activated in human cells?
In mice, the non-canonical inflammasome is activated by direct sensing of cytosolic bacterial lipopolysaccharide (LPS) by caspase-11, which subsequently induces pyroptotic cell death. In human cells, the corresponding caspases of the non-canonical inflammasome are caspase 4 and caspase 5.