PMID- 35630356 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220716 IS - 2076-2607 (Print) IS - 2076-2607 (Electronic) IS - 2076-2607 (Linking) VI - 10 IP - 5 DP - 2022 Apr 26 TI - Salmonella Enteritidis GalE Protein Inhibits LPS-Induced NLRP3 Inflammasome Activation. LID - 10.3390/microorganisms10050911 [doi] LID - 911 AB - Microbial infection can trigger the assembly of inflammasomes and promote secretion of cytokines, such as IL-1beta and IL-18. It is well-known that Salmonella modulates the activation of NLRC4 (NLR family CARD domain-containing protein 4) and NLRP3 (NLR family pyrin domain-containing 3) inflammasomes, however the mechanisms whereby Salmonella avoids or delays inflammasome activation remain largely unknown. Therefore, we used Salmonella Enteritidis C50336DeltafliC transposon library to screen for genes involved in modulating inflammasomes activation. The screen revealed the galactose metabolism-related gene galE to be essential for inflammasome activation. Here, we found that inflammasome activation was significantly increased in J774A.1 cells or wild-type bone marrow-derived macrophages (BMDMs) during infection by DeltafliCDeltagalE compared to cells infected with DeltafliC. Importantly, we found that secretion of IL-1beta was Caspase-1-dependent, consistent with canonical NLRP3 inflammasome activation. Furthermore, the virulence of DeltafliCDeltagalE was significantly decreased compared to DeltafliC in a mouse model. Finally, RNA-seq analysis showed that multiple signaling pathways related to the inflammasome were subject to regulation by GalE. Taken together, our results suggest that GalE plays an important role in the regulatory network of Salmonella evasion of inflammasome activation. FAU - Huang, Tingting AU - Huang T AD - Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou 225009, China. AD - Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou 225009, China. AD - Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agrifood Safety and Quality, Ministry of Agriculture of China, Yangzhou University, Yangzhou 225009, China. AD - Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education, Yangzhou University, Yangzhou 225009, China. FAU - Gu, Dan AU - Gu D AD - Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou 225009, China. AD - Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou 225009, China. AD - Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agrifood Safety and Quality, Ministry of Agriculture of China, Yangzhou University, Yangzhou 225009, China. AD - Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education, Yangzhou University, Yangzhou 225009, China. FAU - Guo, Yaxin AU - Guo Y AD - Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou 225009, China. AD - Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou 225009, China. AD - Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agrifood Safety and Quality, Ministry of Agriculture of China, Yangzhou University, Yangzhou 225009, China. AD - Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education, Yangzhou University, Yangzhou 225009, China. FAU - Li, Ang AU - Li A AD - Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou 225009, China. AD - Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou 225009, China. AD - Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agrifood Safety and Quality, Ministry of Agriculture of China, Yangzhou University, Yangzhou 225009, China. AD - Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education, Yangzhou University, Yangzhou 225009, China. FAU - Kang, Xilong AU - Kang X AD - Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou 225009, China. AD - Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou 225009, China. AD - Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agrifood Safety and Quality, Ministry of Agriculture of China, Yangzhou University, Yangzhou 225009, China. AD - Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education, Yangzhou University, Yangzhou 225009, China. FAU - Jiao, Xinan AU - Jiao X AUID- ORCID: 0000-0002-2214-3358 AD - Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou 225009, China. AD - Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou 225009, China. AD - Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agrifood Safety and Quality, Ministry of Agriculture of China, Yangzhou University, Yangzhou 225009, China. AD - Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education, Yangzhou University, Yangzhou 225009, China. FAU - Pan, Zhiming AU - Pan Z AD - Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou 225009, China. AD - Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou 225009, China. AD - Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agrifood Safety and Quality, Ministry of Agriculture of China, Yangzhou University, Yangzhou 225009, China. AD - Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education, Yangzhou University, Yangzhou 225009, China. LA - eng GR - 31972685, 32161143011 and 31902278/National Natural Science Foundation of China/ GR - BRA2020002/the fifth phase of "333 project" scientific research project in Jiangsu Province/ PT - Journal Article DEP - 20220426 PL - Switzerland TA - Microorganisms JT - Microorganisms JID - 101625893 PMC - PMC9145252 OTO - NOTNLM OT - GalE OT - NLRP3 inflammasome OT - RNA-seq OT - S. Enteritidis OT - virulence COIS- The authors declare no conflict of interest. EDAT- 2022/05/29 06:00 MHDA- 2022/05/29 06:01 PMCR- 2022/04/26 CRDT- 2022/05/28 01:32 PHST- 2022/04/08 00:00 [received] PHST- 2022/04/23 00:00 [revised] PHST- 2022/04/24 00:00 [accepted] PHST- 2022/05/28 01:32 [entrez] PHST- 2022/05/29 06:00 [pubmed] PHST- 2022/05/29 06:01 [medline] PHST- 2022/04/26 00:00 [pmc-release] AID - microorganisms10050911 [pii] AID - microorganisms-10-00911 [pii] AID - 10.3390/microorganisms10050911 [doi] PST - epublish SO - Microorganisms. 2022 Apr 26;10(5):911. doi: 10.3390/microorganisms10050911.