Aflatoxin B1 Induces Reactive Oxygen Species-Mediated Autophagy and Extracellular Trap Formation in Macrophages

Abstract

Aflatoxins are a group of highly toxic mycotoxins with high carcinogenicity that are commonly found in foods. Aflatoxin B1 (AFB1) is the most toxic member of the aflatoxin family. A recent study reported that AFB1 can induce autophagy, but whether AFB1 can induce extracellular traps (ETs) and the relationships among innate immune responses, reactive oxygen species (ROS), and autophagy and the ETs induced by AFB1 remain unknown. Here, we demonstrated that AFB1 induced a complete autophagic process in macrophages (MΦ) (THP-1 cells and RAW264.7 cells). In addition, AFB1 induced the generation of MΦ ETs (METs) in a dose-dependent manner. In particular, the formation of METs significantly reduced the AFB1 content. Further analysis using specific inhibitors showed that the inhibition of either autophagy or ROS prevented MET formation caused by AFB1, indicating that autophagy and ROS were required for AFB1-induced MET formation. The inhibition of ROS prevented autophagy, indicating that ROS generation occurred upstream of AFB1-induced autophagy. Taken together, these data suggest that AFB1 induces ROS-mediated autophagy and ETs formation and an M1 phenotype in MΦ.

Recent Update: Effects of Aflatoxin in Broiler Chickens

“…Monocyte is the phagocytic mononuclear cells to destroy and recycle tissue debris. The monocytes infiltration in the aflatoxicosis induces external trap formation of macrophages (An et al, 2017).…”

Xanthine oxidase activity exerts pro‐oxidative and pro‐inflammatory effects in serum of silver catfish fed with a diet contaminated with aflatoxin B1

“…According to An et al. (), the augmentation of ROS and NOx levels during intoxication with AFB 1 is associated to cell injury, severe inflammation and tissue damage in several organs, which corroborate the involvement of XO activity and uric acid levels to negative effects during AFB 1 consumption. In summary, the excessive formation of uric acid levels can be considered a mechanism involved in the formation of ROS and NOx, which contribute to oxidative and inflammatory process in fish fed with AFB 1 ‐contaminated diet.…”

Effects of ochratoxin A on ER stress, MAPK signaling pathway and autophagy of kidney and spleen in pigs

“…At the same time, FB1‐induced programmed cell death accompanied with autophagy induction in monkey kidney MARC‐145 cells . Aflatoxin B1 (AFB1)‐induced autophagay in macrophages . However, little data are involved in the effects of OTA on autophagy in pigs.…”

“…21 Aflatoxin B1 (AFB1)induced autophagay in macrophages. 45 However, little data are involved in the effects of OTA on autophagy in pigs. The present study showed that dietary supplementation of OTA increased autophgayrelated gene Atg5 and LC3 II expression in kidney and spleen, consistent with previous studies about other mycotoxin that AFB1 or DON or HT2 could induce Atg5 and LC3 II expression in macrophages 45 or in porcine intestinal cells 20 or in porcine oocytes.…”

“…45 However, little data are involved in the effects of OTA on autophagy in pigs. The present study showed that dietary supplementation of OTA increased autophgayrelated gene Atg5 and LC3 II expression in kidney and spleen, consistent with previous studies about other mycotoxin that AFB1 or DON or HT2 could induce Atg5 and LC3 II expression in macrophages 45 or in porcine intestinal cells 20 or in porcine oocytes. 46 In conclusion, this study verified the nephrotoxicity and immuno- OTA and ER stress, p38, and ERK1/2 MAPK signaling pathway and autophagy in pigs.…”