Human NLRP3 inflammasome senses multiple types of bacterial RNAs

被引：108

作者：

Sha, Wenwen ^{[1
,2
]}

Mitoma, Hiroki ^{[2
,3
]}

Hanabuchi, Shino ^{[2
,4
]}

Bao, Musheng ^{[2
,4
]}

Weng, Leiyun ^{[2
]}

Sugimoto, Naoshi ^{[2
,5
]}

Liu, Ying ^{[2
,6
]}

Zhang, Zhiqiang ^{[1
,2
,7
,8
]}

Zhong, Jin ^{[1
]}

Sun, Bing ^{[1
]}

Liu, Yong-Jun ^{[1
,2
,4
]}

机构：

[1] Chinese Acad Sci, Inst Pasteur Shanghai, Key Lab Mol Virol & Immunol, Shanghai 200031, Peoples R China

[2] Baylor Inst Immunol Res, Baylor Scott & White Hlth Serv, Dallas, TX 75204 USA

[3] Kyushu Univ Hosp, Dept Clin Immunol & Rheumatol Infect Dis, Higashi Ku, Fukuoka 8128582, Japan

[4] MedImmune, Gaithersburg, MD 20878 USA

[5] Kyoto Univ, Grad Sch Med, Dept Hematol & Oncol, Kyoto 6068507, Japan

[6] Chinese Acad Sci, Inst Biophys, Key Lab Infect & Immun, Beijing 100101, Peoples R China

[7] Houston Methodist Hosp, Houston, TX 77030 USA

[8] Texas Med Ctr, Houston Methodist Res Inst, Houston, TX 77030 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2014年 / 111卷 / 45期

基金：

美国国家卫生研究院;

关键词：

bacterial RNA; single-stranded RNA; NLRP3; inflammasome; innate immunity; primary macrophages; CYTOPLASMIC DNA; CUTTING EDGE; STRANDED-RNA; ACTIVATION; RECOGNITION; INTERLEUKIN-1-BETA; CRYOPYRIN/NALP3; MACROPHAGES; CASPASE-1; INFECTION;

D O I：

10.1073/pnas.1412487111

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Inflammasomes are multiprotein platforms that activate caspase-1, which leads to the processing and secretion of the proinflammatory cytokines IL-1 beta 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.

引用

页码：16059 / 16064

页数：6

共 35 条

[1] The NLRP3 Inflammasome Mediates In Vivo Innate Immunity to Influenza A Virus through Recognition of Viral RNA [J].