Human NLRP3 Inflammasome senses multiple types of bacterial RNAs

Wenwen Sha, Hiroki Mitoma, Shino Hanabuchi, Musheng Bao, Leiyun Weng, Naoshi Sugimoto, Ying Liu, Zhiqiang Zhang, Jin Zhong, Bing Sun, Yong Jun Liu

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58 Citations (Scopus)

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-repeatcontaining 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.

Original languageEnglish
Pages (from-to)16059-16064
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number45
DOIs
Publication statusPublished - Nov 11 2014

All Science Journal Classification (ASJC) codes

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    Sha, W., Mitoma, H., Hanabuchi, S., Bao, M., Weng, L., Sugimoto, N., Liu, Y., Zhang, Z., Zhong, J., Sun, B., & Liu, Y. J. (2014). Human NLRP3 Inflammasome senses multiple types of bacterial RNAs. Proceedings of the National Academy of Sciences of the United States of America, 111(45), 16059-16064. https://doi.org/10.1073/pnas.1412487111