Sha Wenwen, Mitoma Hiroki, Hanabuchi Shino, Bao Musheng, Weng Leiyun, Sugimoto Naoshi, Liu Ying, Zhang Zhiqiang, Zhong Jin, Sun Bing, Liu Yong-Jun
Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China; Baylor Institute for Immunology Research, Baylor Scott & White Health Service, Dallas, TX 75204;
Baylor Institute for Immunology Research, Baylor Scott & White Health Service, Dallas, TX 75204; Department of Clinical Immunology and Rheumatology/Infectious Disease, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan;
Proc Natl Acad Sci U S A. 2014 Nov 11;111(45):16059-64. doi: 10.1073/pnas.1412487111. Epub 2014 Oct 29.
Inflammasomes are multiprotein platforms that activate caspase-1, which leads to the processing and secretion of the proinflammatory cytokines IL-1β and IL-18. Previous studies demonstrated that bacterial RNAs activate the nucleotide-binding domain, leucine-rich-repeat-containing family, pyrin domain-containing 3 (NLRP3) inflammasome in both human and murine macrophages. Interestingly, only mRNA, but neither tRNA nor rRNAs, derived from bacteria could activate the murine Nlrp3 inflammasome. Here, we report that all three types of bacterially derived RNA (mRNA, tRNA, and rRNAs) were capable of activating the NLRP3 inflammasome in human macrophages. Bacterial RNA's 5'-end triphosphate moieties, secondary structure, and double-stranded structure were dispensable; small fragments of bacterial RNA were sufficient to activate the inflammasome. In addition, we also found that 20-guanosine ssRNA can activate the NLRP3 inflammasome in human macrophages but not in murine macrophages. Therefore, human and murine macrophages may have evolved to recognize bacterial cytosolic RNA differently during bacterial infections.
炎性小体是激活半胱天冬酶 -1的多蛋白平台，这会导致促炎细胞因子白细胞介素 -1β和白细胞介素 -18的加工和分泌。先前的研究表明，细菌RNA可在人类和小鼠巨噬细胞中激活含核苷酸结合域、富含亮氨酸重复序列家族、含吡啉结构域3（NLRP3）的炎性小体。有趣的是，源自细菌的只有mRNA能够激活小鼠Nlrp3炎性小体，而tRNA和rRNA均不能。在此，我们报告所有三种类型的细菌衍生RNA（mRNA、tRNA和rRNA）都能够激活人类巨噬细胞中的NLRP3炎性小体。细菌RNA的5'-端三磷酸基团、二级结构和双链结构并非必需；细菌RNA的小片段就足以激活炎性小体。此外，我们还发现20-鸟苷单链RNA可激活人类巨噬细胞中的NLRP3炎性小体，但不能激活小鼠巨噬细胞中的该炎性小体。因此，在细菌感染期间，人类和小鼠巨噬细胞可能已进化出不同的识别细菌胞质RNA的方式。
