Streptococcus pneumoniae Stimulates a STING- and IFN Regulatory Factor 3-Dependent Type I IFN Production in Macrophages, which Regulates RANTES Production in Macrophages, Cocultured Alveolar Epithelial Cells, and Mouse Lungs
Streptococcus pneumoniae Stimulates a STING- and IFN Regulatory Factor 3-Dependent Type I IFN Production in Macrophages, which Regulates RANTES Production in Macrophages, Cocultured Alveolar Epithelial Cells, and Mouse Lungs
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DOI：
10.4049/jimmunol.1004143
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发表时间：
2012-01-15
影响因子：
4.4
通讯作者：
Opitz, Bastian
中科院分区：
文献类型：
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作者：
Koppe, Uwe;Hoegner, Katrin;Opitz, Bastian
肺炎链球菌是社区获得性肺炎的主要原因。在这项研究中，我们研究了一种感知肺炎球菌感染、触发I型IFN产生和调节RANTES产生的先天免疫识别途径。我们发现人类和小鼠肺泡巨噬细胞以及小鼠骨髓巨噬细胞，而不是肺泡上皮细胞，在感染肺炎链球菌后产生I型ifn。这种反应依赖于成孔毒素溶气素，似乎是由细胞质dna感应途径介导的，涉及适配器分子STING和转录因子IFN调节因子3。事实上，在肺炎球菌感染期间，DNA存在于细胞质中，这是由AIM2炎性小体的激活所表明的，AIM2炎性小体可以感知微生物DNA。肺炎链球菌感染的巨噬细胞产生的I型ifn在体外正调控巨噬细胞和共培养肺泡上皮细胞的基因表达和RANTES的产生。此外，I型干扰素在体内控制肺炎球菌肺炎期间RANTES的产生。总之，我们确定了一种检测肺炎链球菌的免疫传感途径，该途径可触发I型IFN反应并积极调节RANTES的产生。免疫学杂志，2012,18(8):811-817。
Streptococcus pneumoniae is the leading cause of community-acquired pneumonia. In this study, we examine an innate immune recognition pathway that senses pneumococcal infection, triggers type I IFN production, and regulates RANTES production. We found that human and murine alveolar macrophages as well as murine bone marrow macrophages, but not alveolar epithelial cells, produced type I IFNs upon infection with S. pneumoniae. This response was dependent on the pore-forming toxin pneumolysin and appeared to be mediated by a cytosolic DNA-sensing pathway involving the adapter molecule STING and the transcription factor IFN regulatory factor 3. Indeed, DNA was present in the cytosol during pneumococcal infection as indicated by the activation of the AIM2 inflammasome, which is known to sense microbial DNA. Type I IFNs produced by S. pneumoniae-infected macrophages positively regulated gene expression and RANTES production in macrophages and cocultured alveolar epithelial cells in vitro. Moreover, type I IFNs controlled RANTES production during pneumococcal pneumonia in vivo. In conclusion, we identified an immune sensing pathway detecting S. pneumoniae that triggers a type I IFN response and positively regulates RANTES production. The Journal of Immunology, 2012, 188: 811-817.