Publications by authors named "Leana Gorse"
Mechanistic basis for potassium efflux-driven activation of the human NLRP1 inflammasome.
Proc Natl Acad Sci U S A
January 2024
Nigericin, an ionophore derived from , is arguably the most commonly used tool compound to study the NLRP3 inflammasome. Recent findings, however, showed that nigericin also activates the NLRP1 inflammasome in human keratinocytes. In this study, we resolve the mechanistic basis of nigericin-driven NLRP1 inflammasome activation.
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- Scientists found that a specific part of our immune system, called the NLRP1 inflammasome, can detect a harmful substance called exotoxin A produced by a bacterium named Pseudomonas aeruginosa, which can cause chronic infections.
- This exotoxin attacks a protein in our cells, leading to stress and activating the NLRP1 inflammasome, which can cause further cell damage.
- In people with cystic fibrosis, the cells were more sensitive to this exotoxin, showing increased damage, but using certain inhibitors could help reduce this sensitivity.
Article Synopsis
- Neutrophils play a crucial role in fighting infections through various regulated cell death programs, but they are generally seen as ineffective in triggering a specific type of cell death called Caspase-1-dependent pyroptosis.
- Research revealed that certain strains of the bacteria Pseudomonas aeruginosa can actually induce this pyroptosis in neutrophils, particularly when specific exotoxins are deleted, leading to increased neutrophil death.
- The study highlights a mechanism where P. aeruginosa's Flagellin activates a specific inflammasome pathway, resulting in the secretion of interleukin-1β and neutrophil pyroptosis, ultimately demonstrating that neutrophils can indeed undergo this type of cell death.