RIG-I contributes to dsDNA-induced innate immune activation in human brain microvascular endothelial cells

• DOI: 10.1016/j.molimm.2022.10.009
• Publication Date: 2022-10-25T22:01:52Z
• Authors: Zicheng Huang; Xiqiu Xu; Jiapeng Li; Lixing Gu; Yunqiang Yue; Fan Sun; Xiaoyu Zhang; Tongcun Zhang; Yu Liu
• Keywords: TLR3; Human brain

Human brain microvascular epithelial cells (HBMECs) play a pivotal role in maintaining the stability of the blood-brain barrier (BBB), a potent physiological barrier to prevent the invasion of exotic pathogens. Our previous study indicated that polyI:C, an analog of double-stranded RNA (dsRNA), could initiate the TLR3/IFNs antiviral signaling pathway in HBMECs. However, the response of HBMECs to dsDNA remains unclear. In this study, we demonstrated that a dsDNA mimic, poly(dA:dT), could induce the production of a series of antiviral factors, including IFN-β, IFN-λ1, and ISGs. Furthermore, the poly(dA:dT)-activated HBMECs could effectively restrain HSV-1 replication. In addition, we found that RIG-I rather than cGAS and IFI16 had a more crucial role in sensing poly(dA:dT). These observations indicate that HBMECs possess a dsDNA sensing system, and RIG-I may partly contribute to the dsDNA-induced antiviral innate immunity.