Subjects: Biology >> Biophysics >> Immunology submitted time 2016-05-12
Guo, Hao
Zhang, Jialong
Zhang, Xuyuan
Wang, Yanbing
Yu, Haisheng
Yin, Xiangyun
Li, Jingyun
Du, Peishuang
Chen, Jianzhu
Su, Lishan
Liu, Yongjun
Zhang, Liguo
Guo, Hao
Zhang, Xuyuan
Yu, Haisheng
Yin, Xiangyun
Li, Jingyun
Plumas, Joel
Chaperot, Laurence
Chen, Jianzhu
Abstract： Scavenger receptor class B, member 2 (SCARB2) is essential for endosome biogenesis and reorganization and serves as a receptor for both beta-glucocerebrosidase and enterovirus 71. However, little is known about its function in innate immune cells. In this study, we show that, among human peripheral blood cells, SCARB2 is most highly expressed in plasmacytoid dendritic cells (pDCs), and its expression is further upregulated by CpG oligodeoxynucleotide stimulation. Knockdown of SCARB2 in pDC cell line GEN2.2 dramatically reduces CpG-induced type I IFN production. Detailed studies reveal that SCARB2 localizes in late endosome/lysosome of pDCs, and knockdown of SCARB2 does not affect CpG oligodeoxynucleotide uptake but results in the retention of TLR9 in the endoplasmic reticulum and an impaired nuclear translocation of IFN regulatory factor 7. The IFN-I production by TLR7 ligand stimulation is also impaired by SCARB2 knockdown. However, SCARB2 is not essential for influenza virus or HSV-induced IFN-I production. These findings suggest that SCARB2 regulates TLR9-dependent IFN-I production of pDCs by mediating endosomal translocation of TLR9 and nuclear translocation of IFN regulatory factor 7.
Peer Review Status:
Awaiting Review
Subjects: Biology >> Biophysics >> Immunology submitted time 2016-05-05
Zhu, Danming
Liu, Longchao
Yang, Dan
Bian, Yingjie
Sun, Zhichen
He, Junming
Zhang, Liguo
Peng, Hua
Fu, Yang-Xin
Liu, Longchao
Bian, Yingjie
Sun, Zhichen
Fu, Sherry
Fu, Yang-Xin
Su, Lishan
Abstract： Development of therapeutic vaccines/strategies to control chronic hepatitis B virus (HBV) infection has been challenging because of HBV-induced tolerance. In this study, we explored strategies for breaking tolerance and restoring the immune response to the HBV surface Ag in tolerant mice. We demonstrated that immune tolerance status is attributed to the level and duration of circulating HBsAg in HBV carrier models. Removal of circulating HBsAg by a monoclonal anti-HBsAg Ab in tolerant mice could gradually reduce tolerance and reestablish B cell and CD4(+) T cell responses to subsequent Engerix-B vaccination, producing protective IgG. Furthermore, HBsAg-specific CD8(+) T cells induced by the addition of a TLR agonist resulted in clearance of HBV in both serum and liver. Thus, generation of protective immunity can be achieved by clearing extracellular viral Ag with neutralizing Abs followed by vaccination.
Peer Review Status:Awaiting Review
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