Scientists capture how cells trigger inflammation

Amazing stuff!

"In brief

• SLAC researchers observed a key master regulator of inflammation inside living cells, revealing a dense, gel-like structure that is much less organized than expected.
• The findings suggest this inflammation-triggering system forms a flexible cluster of proteins, which could influence the design of treatments for inflammatory diseases.
• The study also revealed a link between inflammation and the machinery that controls cell division, suggesting a possible explanation for why cells usually stop dividing while mounting an inflammatory response.

... to capture, for the first time, the formation of an immune signaling complex inside intact human cells.

The results ... provide a closer look at how the complex assembles and interacts with other parts of the cell, offering new insight into the early stages of the body’s inflammatory response to infection and other stress signals. Their work, which challenges longstanding models of the process, could help guide future efforts to develop new therapeutic approaches for inflammatory diseases. ..."

From the abstract:

"The NLRP3 inflammasome is a multiprotein molecular machine that drives inflammatory responses in innate immunity. Although its dysregulation is implicated in numerous human diseases, its structural organization in cells remains poorly understood.

Here, we used precise fluorescence-guided cryo–focused ion beam (cryo-FIB) milling and cryo–electron tomography (cryo-ET) to visualize NLRP3 inflammasomes in situ within human macrophages at various stages of activation.

After priming and activation, we observed expansion and dispersion of Golgi cisternae, along with the emergence of 50-nanometer NLRP3-associated vesicles, which likely transport NLRP3 to the MTOC.

Dense NLRP3-containing condensates then formed in and around the MTOC. In later stages, the condensates solidified, coincident with widespread mitochondrial damage, autophagy, and pyroptotic cell death."

Scientists capture how cells trigger inflammation | Stanford Report "SLAC scientists observed an immune signaling complex forming inside cells for the first time, revealing insights that could guide new treatments."

Human NLRP3 inflammasome activation leads to formation of condensate at the microtubule organizing center (open access)

Fig. 1. Progression of NLRP3 inflammasome activation.