bims-nocaut Biomed News
on Non-canonical autophagy
Issue of 2024–05–19
two papers selected by
Quentin Frenger, University of Strasbourg
  1. CALCOCO2/NDP52 associates with RAB9 to initiate an antiviral response to hepatitis B virus infection through a lysosomal degradation pathway.
  2. Oroxylin A-induced Trained Immunity Promotes LC3-associated Phagocytosis in Macrophage in Protecting Mice Against Sepsis.
  1. Autophagy. 2024 May 16. 1-3
    CALCOCO2/NDP52 associates with RAB9 to initiate an antiviral response to hepatitis B virus infection through a lysosomal degradation pathway.
    Shuzhi Cui, Mathias Faure, Yu Wei.
      CALCOCO2/NDP52 recognizes LGALS8 (galectin 8)-coated invading bacteria and initiates anti-bacterial autophagy by recruiting RB1CC1/FIP200 and TBKBP1/SINTBAD-AZI2/NAP1. Whether CALCOCO2 exerts similar functions against viral infection is unknown. In our recent study we show that CALCOCO2 targets envelope proteins of hepatitis B virus (HBV) to the lysosome for degradation, resulting in inhibition of viral replication. In contrast to anti-bacterial autophagy, lysosomal degradation of HBV does not require either LGALS8 or ATG5, and CALCOCO2 mutants abolishing the formation of the RB1CC1-CALCOCO2-TBKBP1-AZI2 complex maintain their inhibitory function on the virus. CALCOCO2-mediated inhibition depends on RAB9, which is a key factor in the alternative autophagy pathway. CALCOCO2 forms a complex with RAB9 only in the presence of viral envelope proteins and links HBV to the RAB9-dependent lysosomal degradation pathway. These findings reveal a new mechanism by which CALCOCO2 triggers antiviral responses against HBV infection and suggest direct roles for autophagy receptors in other lysosomal degradation pathways than canonical autophagy.
    Keywords:  CALCOCO2/NDP52; RAB9; hepatitis B virus; lysosomal degradation; viral envelop proteins
    DOI:  https://doi.org/10.1080/15548627.2024.2353499
  2. Inflammation. 2024 May 13.
    Oroxylin A-induced Trained Immunity Promotes LC3-associated Phagocytosis in Macrophage in Protecting Mice Against Sepsis.
    Lijie Yin, Ziqian Bing, Yaojun Zheng, Yuchen Pan, Yue Dong, Jiali Wang, Renjie Luo, Yue Zhao, Huan Dou, Yayi Hou.
      Sepsis is defined as a dysregulated host response to infection that leads to multiorgan failure. Innate immune memory, i.e., "trained immunity", can result in stronger immune responses and provide protection against various infections. Many biological agents, including β-glucan, can induce trained immunity, but these stimuli may cause uncontrolled inflammation. Oroxylin A (OA) is an active flavonoid compound that is derived from Scutellaria baicalensis. OA is an agonist for inducing trained immunity in vivo and in vitro, and β-glucan was used as a positive control. The protective effects of OA-induced trained immunity were evaluated in mouse models that were established by either lipopolysaccharide (LPS) administration or caecal ligation and puncture (CLP). The expression of inflammatory factors and signaling pathway components involved in trained immunity was evaluated in vitro using qRT‒PCR, western blotting (WB) and enzyme-linked immunosorbent assay (ELISA). Flow cytometry and confocal microscopy were used to examine reactive oxygen species (ROS) levels and phagocytosis in trained macrophages. A PCR array was used to screen genes that were differentially expressed in trained macrophages. Here, we revealed that OA alleviated sepsis via trained immunity. OA-treated macrophages displayed increased glycolysis and mTOR phosphorylation, and mTOR inhibitors suppressed OA-induced trained immunity by effectively reprogramming macrophages. The PCR array revealed key genes in the mTOR signaling pathway in OA-treated macrophages. Furthermore, OA targeted the Dectin-1-syk axis to promote LC3-associated phagocytosis (LAP) by trained macrophages, thereby enhancing the ability of these macrophages to protect against infection. This ability could be transferred to a new host via the adoptive transfer of peritoneal macrophages. This study is the first to provide new insights into the potential of OA-induced trained immunity to be used as a strategy to protect mice against sepsis by promoting LAP by macrophages.
    Keywords:  LC3-associated phagocytosis; macrophage; oroxylin A; sepsis; trained immunity
    DOI:  https://doi.org/10.1007/s10753-024-02033-2
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