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[M. Immunology-17]
Exclusive traits of neutrophils in NLRP3 inflammasome
signaling contribute to prolonged inflammation
SeungHwan Son¹, Inhwa Hwang¹, Je-Wook Yu¹˙*
¹Microbiology and Immunology, Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS
Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
Accumulating evidence suggests importance of neutrophils in the progression of chronic inflammatory disorders,
however a key factor, inflammasome signaling and its aftermath in neutrophils remain obscure. Here we present
exclusive traits of neutrophils in inflammasome signaling contribute to the prolonged inflammation. We showed
neutrophils resist to undergo cell death, including pyroptosis upon inflammasome activation. Consistently, NLRP3
inflammasome activated neutrophils preserved their functional integrity, encompassing phagocytosis and
degranulation. Surprisingly, unlike macrophages, neutrophils under DAMPs-rich condition maintained NLRP3
inflammasome activating potential. Mechanistically, resistance to pyroptosis in neutrophils derived from impaired
GSDMD cleavage along with impaired mitochondrial membrane potential loss. Moreover, DAMP, including ATP
exposed neutrophils conserved mitochondrial membrane potential facilitating NLRP3 inflammasome activation.
Furthermore, unlike apoptotic neutrophils, NLRP3 inflammasome activated neutrophils failed to induce efferocytosis
in peritoneal macrophages. Collectively, neutrophils under DAMP-rich milieu preserve their potential to activate
NLRP3 inflammasome without pyroptosis, compared to macrophages leading prolonged inflammation.
