‘Gut, Liver and Friends’ Seminar with Matthew Mangan

On Wednesday, 21.05.2025 at 12:30, Matthew Mangan from the Institute of Medical Microbiology at Cologne University Hospital will be the speaker of our ‘Gut, Liver and Friends‘ seminar.

The title of his presentation is:

“Cytosolic sodium accumulation is a common danger signal triggering endocytic dysfunction and NLRP3 inflammasome activation“

Detecting noxious molecules within the endo/lysosomal system is essential for maintaining cellular integrity. Here, we identify acute cytosolic sodium accumulation as a key trigger for NLRP3 inflammasome activation. Large clostridial toxins, as well as monosodium urate and silica crystals, rapidly elevate cytosolic sodium by promoting its release from the endo/lysosomal system, triggering potassium efflux and subsequent extracellular sodium influx. This rise in cytosolic sodium disrupts endocytic trafficking by collapsing the sodium gradient across endosomal membranes, leading to peripheral redistribution and activation of NLRP3. Importantly, non-particulate stimuli, including nigericin, also activate NLRP3 by this sodium-dependent mechanism. These findings position cytosolic sodium as a key downstream effector of potassium efflux and a central signal for NLRP3 activation across diverse stimuli.