title: Human NLRP3 inflammasome senses multiple types of bacterial RNAs.
abstract: 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.
authors.affiliation: 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;
authors.forename: Wenwen
authors.initials: W
authors.lastname: Sha
authors.affiliation: 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;
authors.forename: Hiroki
authors.initials: H
authors.lastname: Mitoma
authors.affiliation: Baylor Institute for Immunology Research, Baylor Scott & White Health Service, Dallas, TX 75204; MedImmune, Gaithersburg, MD 20878;
authors.forename: Shino
authors.initials: S
authors.lastname: Hanabuchi
authors.affiliation: Baylor Institute for Immunology Research, Baylor Scott & White Health Service, Dallas, TX 75204; MedImmune, Gaithersburg, MD 20878;
authors.forename: Musheng
authors.initials: M
authors.lastname: Bao
authors.affiliation: Baylor Institute for Immunology Research, Baylor Scott & White Health Service, Dallas, TX 75204;
authors.forename: Leiyun
authors.initials: L
authors.lastname: Weng
authors.affiliation: Baylor Institute for Immunology Research, Baylor Scott & White Health Service, Dallas, TX 75204; Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan;
authors.forename: Naoshi
authors.initials: N
authors.lastname: Sugimoto
authors.affiliation: Baylor Institute for Immunology Research, Baylor Scott & White Health Service, Dallas, TX 75204; The Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; and.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: 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; Immunobiology and Transplant Research, Houston Methodist Hospital and Houston Methodist Research Institute, Texas Medical Center, Houston, TX 77030.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China;
authors.forename: Jin
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China; bsun@sibs.ac.cn liuyo@medimmune.com.
authors.forename: Bing
authors.initials: B
authors.lastname: Sun
authors.affiliation: 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; MedImmune, Gaithersburg, MD 20878; bsun@sibs.ac.cn liuyo@medimmune.com.
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Liu
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000276:immunology*; D045744:Cell Line, Tumor; D006801:Humans; D058847:Inflammasomes / Q000276:immunology*; D020382:Interleukin-18 / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D051379:Mice; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D012329:RNA, Bacterial / Q000276:immunology*; D012333:RNA, Messenger / Q000276:immunology*; D013045:Species Specificity
chemical_list: D002352:Carrier Proteins; C508585:IL1B protein, human; D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D012329:RNA, Bacterial; D012333:RNA, Messenger
keywords: NLRP3 inflammasome; bacterial RNA; innate immunity; primary macrophages; single-stranded RNA