biostudies-literatureWang BNational Natural Science Foundation of China101695https://www.ebi.ac.uk/biostudies/studies/S-EPMC8792265biostudies-literatureUnknown101(3)Fowl adenovirus serotype 4 (FAdV-4) is the primary causative agent of hepatitis-hydropericardium syndrome (HHS) causing great economic losses to the world poultry industry. The exact factors responsible for the pathogenesis of hypervirulent FAdV-4 have not been completely elucidated. Hypervirulent FAdV-4 infection induces inflammatory damages in accompany with a high level of proinflammatory interleukin-1 beta (IL-1β) secretion in a variety of organs. Investigation of the mechanisms underlying hypervirulent FAdV-4-induced IL-1β secretion would contribute to understanding of the pathogenesis of FAdV-4. Here, we investigated whether FAdV-4 infection activates NLRP3 inflammasome in chicken macrophage cell line HD11. The results showed that stimulation of HD11 with hypervirulent FAdV-4 induced NLRP3- and Caspase-1-dependent secretion of IL-1β. Genetic knockdown of NLRP3 or Caspase-1 expression, a critical component of inflammasome, significantly downregulated IL-1β expression, indicating that activation of the NLRP3 inflammasome contributed to the FAdV-4-induced IL-1β secretion. Moreover, ATP signaling and potassium efflux were involved in the process of NLRP3 inflammasome activation. Our data indicated that hypervirulent FAdV-4 infection induces the activation of NLRP3 inflammasome and followed by massive secretion of IL-1β of macrophages, which thereby contribute to the inflamed lesion of tissues.Poultry scienceHypervirulent FAdV-4 infection induces activation of the NLRP3 inflammasome in chicken macrophages.PMC879226531772771Li YSong MWang BGuo HYang PSong CMiao YQiao QHuang QWang ZZhao JfalseHypervirulent FAdV-4 infection induces activation of the NLRP3 inflammasome in chicken macrophages.Fowl adenovirus serotype 4 (FAdV-4) is the primary causative agent of hepatitis-hydropericardium syndrome (HHS) causing great economic losses to the world poultry industry. The exact factors responsible for the pathogenesis of hypervirulent FAdV-4 have not been completely elucidated. Hypervirulent FAdV-4 infection induces inflammatory damages in accompany with a high level of proinflammatory interleukin-1 beta (IL-1β) secretion in a variety of organs. Investigation of the mechanisms underlying hypervirulent FAdV-4-induced IL-1β secretion would contribute to understanding of the pathogenesis of FAdV-4. Here, we investigated whether FAdV-4 infection activates NLRP3 inflammasome in chicken macrophage cell line HD11. The results showed that stimulation of HD11 with hypervirulent FAdV-4 induced NLRP3- and Caspase-1-dependent secretion of IL-1β. Genetic knockdown of NLRP3 or Caspase-1 expression, a critical component of inflammasome, significantly downregulated IL-1β expression, indicating that activation of the NLRP3 inflammasome contributed to the FAdV-4-induced IL-1β secretion. Moreover, ATP signaling and potassium efflux were involved in the process of NLRP3 inflammasome activation. Our data indicated that hypervirulent FAdV-4 infection induces the activation of NLRP3 inflammasome and followed by massive secretion of IL-1β of macrophages, which thereby contribute to the inflamed lesion of tissues.2022-01-01T00:00:00Z2022 Mar2025-04-04T07:52:08.669Z2025-04-04T07:52:08.669ZS-EPMC87922653507792210.1016/j.psj.2021.101695