Neutrophil extracellular traps formation and autophagy in bongkrekic acid exposed human neutrophils

Bongkrekic acid (BKA), a less well-known foodborne toxin, has been implicated in numerous poisoning incidents. Recent studies suggest that BKA exerts an impact on the immune system, particularly on innate immunity. The release of neutrophil extracellular traps (NETs) is relatively a newly-discovered mechanism involving innate immunity. This study was designed to characterize and evaluate the effects of BKA on human NET formation. The co-localization of DNA, histones, and myeloperoxidase (MPO) was determined via immunostaining to confirm BKA-triggered NET formation in human neutrophils. NET quantification showed that NET formation induced by BKA was both time- and dose-dependent, and was associated with p38, ERK, PAD4 and P2X1 receptor. Moreover, immunostaining analysis observed that BKA triggered both NET formation and autophagy. Additionally, pharmacological experiments revealed that autophagy mediated BKA-triggered NET formation. Collectively, these insights offer a novel perspective on the effects of BKA exposure on host's innate immune response, and may shed new light on BKA poisoning. We call for further work to be conducted in this field to unravel the intricate mechanisms governing NET formation and autophagy in the context of BKA poisoning.