Introduction:  NLRP3 inflammasome is an important player in innate immunity. Extracellular Traps (NETs), are newly described neutrophils killing mechanism, are composed by a DNA backbone and multiple functional proteins, formed via a process known as NETosis. Autophagy is a vital cellular mechanism responsible for recycling and removal of damaged proteins and organelles, as well as destruction of intracellular pathogens. The process of NETosis is largely unknown, now a large of evidences have suggested that autophagy may be involved in NETs formation. 

Methods : We compared NETosis between neutrophils from WT and NLRP3 gene deficient mouse as well as human neutrophils treated with and without NLRP3 inhibitor in vivo and in vitro. NETs formation, autophagy activation markers, ROS , Citrullinated histone H3 and PAD4 were compared were analyzed in NLRP3−/− and wild-type neutrophils stimulated in vitro with E.coli and in vivo during sepsis. NETs formation were compared using autophagy inhibitor as well as autophagy inducer. 

Results: We found that autophagy and NRLP3 were required for NETs formation. Moreover, NLRP3 partly mediated NETs formation in vitro and in vivo during sepsis. We also showed that attenuated NETs formation in NLRP3−/− neutrophils correlated with an impaired autophagy activation. 

Conclusions:  NLRP3 regulates autophagy to control NETs formation during sepsis