PMID- 32922370 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200928 IS - 1664-302X (Print) IS - 1664-302X (Electronic) IS - 1664-302X (Linking) VI - 11 DP - 2020 TI - Contribution of Nlrp3 Inflammasome Activation Mediated by Suilysin to Streptococcal Toxic Shock-like Syndrome. PG - 1788 LID - 10.3389/fmicb.2020.01788 [doi] LID - 1788 AB - Objective: The aim of this study was to investigate the molecular mechanism of inflammasome activation in response to Streptococcus suis serotype 2 (SS2) infection and its contribution to the development of streptococcal toxic shock-like syndrome (STSS). Methods: To verify the role of suilysin (SLY) in STSS, we infected bone-marrow-derived macrophages (BMDMs) in vitro and C57BL/6J mice intraperitoneally (IP) with the SS2 wild-type (WT) strain or isogenic sly mutant (∆SLY) to measure the interleukin (IL)-1beta release and survival rate. To determine the role of inflammasome activation and pyroptosis in STSS, we infected BMDMs from WT and various deficient mice, including Nlrp3-deficient (Nlrp3(-/-)), Nlrc4-deficient (Nlrc4(-/-)), Asc-deficient (Asc(-/-)), Aim2-deficient (Aim2(-/-)), Caspase-1/11-deficient (Caspase-1/11(-/-)), and Gsdmd-deficient (Gsdmd(-/-)) ex vivo, and IP injected WT, Nlrp3(-/-), Caspase-1/11(-/-), and Gsdmd(-/-) mice with SS2, to compare the IL-1beta releases and survival rate in vivo. Results: The SS2-induced IL-1beta production in mouse macrophages is mediated by SLY ex vivo. The survival rate of WT mice infected with SS2 was significantly lower than that of mice infected with the ∆SLY strain in vivo. Furthermore, SS2-triggered IL-1beta releases, and the cytotoxicity in the BMDMs required the activation of the NOD-Like Receptors Family Pyrin Domain Containing 3 (Nlrp3), Caspase-1/11, and gasdermin D (Gsdmd) inflammasomes, but not the Nlrc4 and Aim2 inflammasomes ex vivo. The IL-1beta production and survival rate of WT mice infected with SS2 were significantly lower than those of the Nlrp3(-/-), Caspase-1/11(-/-), and Gsdmd(-/-) mice in vivo. Finally, the inhibitor of the Nlrp3 inflammasome could reduce the IL-1beta release and cytotoxicity of SS2-infected macrophages ex vivo and protect SS2-infected mice from death in vivo. Conclusion: Nlrp3 inflammasome activation triggered by SLY in macrophages played an important role in the pathogenesis of STSS. CI - Copyright (c) 2020 Song, Li, Xiao, Huang, Jiang, Meng and Ren. FAU - Song, Liqiong AU - Song L AD - State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention, Beijing, China. AD - Research Units of Discovery of Unknown Bacteria and Function (2018 RU010), Chinese Academy of Medical Sciences, Beijing, China. FAU - Li, Xianping AU - Li X AD - State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention, Beijing, China. AD - Research Units of Discovery of Unknown Bacteria and Function (2018 RU010), Chinese Academy of Medical Sciences, Beijing, China. FAU - Xiao, Yuchun AU - Xiao Y AD - State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention, Beijing, China. AD - Research Units of Discovery of Unknown Bacteria and Function (2018 RU010), Chinese Academy of Medical Sciences, Beijing, China. FAU - Huang, Yuanming AU - Huang Y AD - State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention, Beijing, China. AD - Research Units of Discovery of Unknown Bacteria and Function (2018 RU010), Chinese Academy of Medical Sciences, Beijing, China. FAU - Jiang, Yongqiang AU - Jiang Y AD - State Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing, China. FAU - Meng, Guangxun AU - Meng G AD - The Center for Microbes, Development and Health, CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China. FAU - Ren, Zhihong AU - Ren Z AD - State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention, Beijing, China. AD - Research Units of Discovery of Unknown Bacteria and Function (2018 RU010), Chinese Academy of Medical Sciences, Beijing, China. LA - eng PT - Journal Article DEP - 20200814 PL - Switzerland TA - Front Microbiol JT - Frontiers in microbiology JID - 101548977 PMC - PMC7456889 OTO - NOTNLM OT - Streptococcus suis OT - caspase-1 OT - inflammasome OT - interlukin-1beta OT - suilysin EDAT- 2020/09/15 06:00 MHDA- 2020/09/15 06:01 PMCR- 2020/08/14 CRDT- 2020/09/14 05:50 PHST- 2020/04/07 00:00 [received] PHST- 2020/07/08 00:00 [accepted] PHST- 2020/09/14 05:50 [entrez] PHST- 2020/09/15 06:00 [pubmed] PHST- 2020/09/15 06:01 [medline] PHST- 2020/08/14 00:00 [pmc-release] AID - 10.3389/fmicb.2020.01788 [doi] PST - epublish SO - Front Microbiol. 2020 Aug 14;11:1788. doi: 10.3389/fmicb.2020.01788. eCollection 2020.