Functional proteomic profiling links deficient DNA clearance with increased mortality in individuals with severe COVID-19 pneumonia
Iker Valle Aramburu, Dennis Hoving, Spyros I Vernardis, Martha CF Tin, Marianna Ioannou, Mia I Temkin, Nathalia M De Vasconcelos, Vadim Demichev, Elisa Theresa Helbig, Lena Lippert, Klaus Stahl, Matthew White, Helena Radbruch, Jana Ihlow, David Horst, Scott T Chiesa, John E Deanfield, Sascha David, Christian Bode, Florian Kurth, Markus Ralser & Venizelos Papayannopoulos
The factors that influence survival during severe infection are unclear. Extracellular chromatin drives pathology, but the mechanisms enabling its accumulation remain elusive. Here, we show that in murine sepsis models, splenocyte death interferes with chromatin clearance through the release of the DNase I inhibitor actin. Actin-mediated inhibition was compensated by upregulation of DNase I or the actin scavenger gelsolin. Splenocyte death and neutrophil extracellular trap (NET) clearance deficiencies were prevalent in individuals with severe COVID-19...
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