Key Laboratory of Infection and Immunity of Shandong Province & Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University, Jinan 250012, Shandong, P.R. China; Department of Pathogenic Biology, School of Biomedical Sciences, Shandong University, Jinan 250012, Shandong, P.R. China.
Key Laboratory of Infection and Immunity of Shandong Province & Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University, Jinan 250012, Shandong, P.R. China; Department of Immunology, School of Biomedical Sciences, Shandong University, Jinan 250012, Shandong, P.R. China.
Immunity. 2023 Aug 8;56(8):1727-1742.e6. doi: 10.1016/j.immuni.2023.06.002. Epub 2023 Jun 27.
STING (stimulator of interferon genes) exerts protective cellular responses to viral infection via induction of interferon production and autophagy. Here, we report the role of STING in modulating the immune responses toward fungal infection. Upon Candida albicans stimulation, STING transited alongside the endoplasmic reticulum (ER) to the phagosomes. In phagosomes, STING directly bound with Src via the N-terminal 18 amino acids of STING, and this binding prevented Src from recruiting and phosphorylating Syk. Consistently, Syk-associated signaling and production of pro-inflammatory cytokines and chemokines were increased in mouse BMDCs (bone-marrow-derived dendritic cells) lacking STING with fungal treatment. STING deficiency improved anti-fungal immunity in systemic C. albicans infection. Importantly, administration of the N-terminal 18-aa (amino acid) peptide of STING improved host outcomes in disseminated fungal infection. Overall, our study identifies a previously unrecognized function of STING in negatively regulating anti-fungal immune responses and offers a potential therapeutic strategy for controlling C. albicans infection.
STING（干扰素基因刺激物）通过诱导干扰素产生和自噬来发挥对病毒感染的保护细胞反应。在这里，我们报告了 STING 在调节针对真菌感染的免疫反应中的作用。在白色念珠菌刺激下，STING 与内质网（ER）一起转移到吞噬体。在吞噬体中，STING 通过 STING 的 N 端 18 个氨基酸直接与Src 结合，这种结合阻止 Src 招募和磷酸化 Syk。一致地，在真菌处理的缺乏 STING 的小鼠 BMDCs（骨髓来源的树突状细胞）中，Syk 相关信号转导以及促炎细胞因子和趋化因子的产生增加。STING 缺乏症改善了全身性白色念珠菌感染中的抗真菌免疫。重要的是，STING 的 N 端 18 个氨基酸肽的给药改善了播散性真菌感染中的宿主结局。总的来说，我们的研究确定了 STING 在负调控抗真菌免疫反应中的一个以前未被识别的功能，并为控制白色念珠菌感染提供了一种潜在的治疗策略。
