Joshua Thompson, PhD
Postdoctoral Trainee
Department of Pharmacology & Regenerative Medicine
Advisor: Asrar B Malik, PhD Heading link
Title: Role of the cGAS/STING dsDNA sensor in Neutrophil NET Formation and Immunopathy
Abstract:Trained immunity has the potential to restore tissue homeostasis following repeated pathogen challenges in response to damage- or pathogen-associated molecular patterns, such as ATP. We previously showed that the K+ efflux channel TWIK2 in macrophages activated the NLRP3 inflammasome and consequently mediated inflammation. Here we investigated the role of TWIK2 in driving training of macrophages and its role in augmenting the function of macrophages in response to repeated DAMP/PAMP exposure. We observed that ATP challenge of lung macrophages induced plasma membrane association of TWIK2 lasting up to 2 weeks. The ATP-treated macrophages exhibiting plasmalemmal TWIK2 localization showed enhanced phagosomal K+ influx, phagocytosis, and bacterial killing. These results indicated TWIK2 dependent induction of trained immunity. Macrophage training was sufficient to prevent immunoparalysis observed after repeated pathogen exposure. These findings demonstrate the role of ATP mediated plasmalemmal localization of the K+ efflux channel TWIK2 in training macrophages.