- NEDD4 Regulated Pyroptosis Occurred from Co‑infection between Influenza A Virus and Streptococcus pneumoniae
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Jiangzhou You , Linlin Zhou , Xudong San , Hailing Li , Mingyuan Li , Baoning Wang
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J. Microbiol. 2023;61(8):777-789. Published online October 4, 2023
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DOI: https://doi.org/10.1007/s12275-023-00076-y
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Co-infection of respiratory tract viruses and bacteria often result in excess mortality, especially pneumonia caused by influenza
viruses and Streptococcus pneumoniae. However, the synergistic mechanisms remain poorly understood. Therefore, it
is necessary to develop a clearer understanding of the molecular basis of the interaction between influenza virus and Streptococcus
pneumonia. Here, we developed the BALB/c mouse model and the A549 cell model to investigate inflammation
and pyroptotic cell death during co-infection. Co-infection significantly activated the NLRP3 inflammasome and induced
pyroptotic cell death, correlated with excess mortality. The E3 ubiquitin ligase NEDD4 interacted with both NLRP3 and
GSDMD, the executor of pyroptosis. NEDD4 negatively regulated NLRP3 while positively regulating GSDMD, thereby
modulating inflammation and pyroptotic cell death. Our findings suggest that NEDD4 may play a crucial role in regulating
the GSDMD-mediated pyroptosis signaling pathway. Targeting NEDD4 represents a promising approach to mitigate excess
mortality during influenza pandemics by suppressing synergistic inflammation during co-infection of influenza A virus and
Streptococcus pneumoniae.
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Citations
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