Jelena Bezbradica, Rebecca Coll and Kate Schroder from the Inflammasome Lab have uncovered a hierarchy of inflammasome responses to different types of cellular dangers, suggesting that our immune cells triage danger signals. The discovery was recently accepted for publication in the journal Cellular & Molecular Immunology.
Our immune cells, like macrophages, sense danger through a broad repertoire of immune receptors on the cell's surface. These signalling systems are interconnected through multiple layers of signal cross-talk to inflammasomes inside the cell - protein complexes at the heart of inflammation (eg. illustrated in the image above). Broadly, there are two types of inflammation: inflammation to restore homeostasis following a sterile injury and inflammation in response to a microbial infection, to both eradicate the microbe and induce protective immunity. We performed the first direct side-by-side comparison of NLRP3 inflammasome responses to these two triggers of inflammation. In both mouse and human macrophages, we discovered that sterile signals (TNF and ATP) exhibited delayed and weaker abilities to both prime and activate an NLRP3 response, when compared to microbial priming and activating signals (LPS and nigericin). This discovery, that sterile versus microbial signals trigger distinct responses, may be an important factor in the design of new drugs to treat inflammatory diseases.
Bezbradica JS1, Coll RC1 and Schroder K (2016).
Sterile signals generate weaker and delayed macrophage NLRP3 inflammasome responses relative to microbial signals. Cellular & Molecular Immunology In press. Pubmed
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