Final Report Summary - INFLAMMACT (Activation and Regulation of the NLRP3 Inflammasome)
We have furthermore demonstrated that NLRP3 can be activated by Western diet feeding of mice and that NLRP3 activation in this context mediates bone marrow myeloid precursor activation and proliferation. Importantly, we could demonstrate that the 'recognition' of Western dieting by NLRP3 led to a long-lasting change of cellular responsiveness towards a range of innate immune-activating stimuli in innate immune cells and their myeloid precursors. Thus, we identified that NLRP3 can provoke 'innate immune memory', which could be of importance for the development of chronic inflammatory conditions in metabolic diseases linked to Western diets.
Identifying the exact molecular mechanisms that trigger inflammasome activation by many different activators, however, remains particularly challenging. As of yet, the exact molecular details of NLRP3 activation remain not fully understood. However, our systems pharmacology and proteomics approach combined with novel biochemical techniques led to a better understanding of how NLRP3 is activated.