PDF(Pubmed)
Abstract：
SARS-CoV-2 causes a spectrum of clinical symptoms from respiratory damage to gastrointestinal disorders. Intestinal infection of SARS-CoV-2 triggers immune response. However, the cellular mechanism that how SARS-CoV-2 initiates and induces intestinal immunity is not understood. Here, we exploited SARS-CoV-2-GFP/ΔN trVLP pseudo-virus system and demonstrated that RIG-I and DHX15 are required for sensing SARS-CoV-2 and inducing cellular immune response through MAVS signaling in intestinal epithelial cells (IECs) upon SARS-CoV-2 infection. NLRP6 also engages in the regulation of SARS-CoV-2 immunity by producing IL-18. Furthermore, primary cellular immune response provoked by SARS-CoV-2 in IECs further cascades activation of MAIT cells and produces cytotoxic cytokines including IFN-γ, granzyme B via an IL-18 dependent mechanism. These findings taken together unveil molecular basis of immune recognition in IECs in response to SARS-CoV-2, and provide insights that intestinal immune cross-talk with other immune cells triggers amplified immunity and probably contributes to immunopathogenesis of COVID-19.
摘要：
SARS-CoV-2引起一系列临床症状，包括呼吸道损伤和胃肠道疾病。SARS-CoV-2的肠道感染引发免疫反应。然而,SARS-CoV-2如何启动和诱导肠道免疫的细胞机制尚不清楚。这里,我们利用SARS-CoV-2-GFP/ΔNtrVLP假病毒系统，并证明RIG-I和DHX15是检测SARS-CoV-2并通过肠上皮细胞（IECs）中的MAVS信号传导诱导细胞免疫应答所必需的。SARS-CoV-2感染。NLRP6还通过产生IL-18参与SARS-CoV-2免疫的调节。此外，IECs中SARS-CoV-2引起的初级细胞免疫反应进一步级联激活MAIT细胞并产生细胞毒性细胞因子，包括IFN-γ，颗粒酶B通过IL-18依赖性机制。这些发现共同揭示了响应SARS-CoV-2的IEC中免疫识别的分子基础，并提供了与其他免疫细胞的肠道免疫串扰触发增强免疫力的见解，并可能有助于COVID-19的免疫发病机制。
