PMID- 38477589
OWN - NLM
STAT- MEDLINE
DCOM- 20240410
LR  - 20240411
IS  - 1098-5522 (Electronic)
IS  - 0019-9567 (Print)
IS  - 0019-9567 (Linking)
VI  - 92
IP  - 4
DP  - 2024 Apr 9
TI  - Salmonella Enteritidis antitoxin DinJ inhibits NLRP3-dependent canonical 
      inflammasome activation in macrophages.
PG  - e0050523
LID - 10.1128/iai.00505-23 [doi]
LID - e00505-23
AB  - The inflammasome is a pivotal component of the innate immune system, acting as a 
      multiprotein complex that plays an essential role in detecting and responding to 
      microbial infections. Salmonella Enteritidis have evolved multiple mechanisms to 
      regulate inflammasome activation and evade host immune system clearance. Through 
      screening S. Enteritidis C50336DeltafliC transposon mutant library, we found that the 
      insertion mutant of dinJ increased inflammasome activation. In this study, we 
      demonstrated the genetic connection between the antitoxin DinJ and the toxin YafQ 
      in S. Enteritidis, confirming their co-transcription. The deletion mutant 
      DeltafliCDeltadinJ increased cell death and IL-1beta secretion in J774A.1 cells. Western 
      blotting analysis further showed elevated cleaved Caspase-1 product (p10 
      subunits) and IL-1beta secretion in cells infected with DeltafliCDeltadinJ compared to cells 
      infected with DeltafliC. DinJ was found to inhibit canonical inflammasome activation 
      using primary bone marrow-derived macrophages (BMDMs) from Casp(-/-) C57BL/6 
      mice. Furthermore, DinJ specifically inhibited NLRP3 inflammasome activation, as 
      demonstrated in BMDMs from Nlrp3(-/-) and Nlrc4(-/-) mice. Fluorescence resonance 
      energy transfer (FRET) experiments confirmed the translocation of DinJ into host 
      cells during infection. Finally, we revealed that DinJ could inhibit the 
      secretion of IL-1beta and IL-18 in vivo, contributing to S. Enteritidis evading host 
      immune clearance. In summary, our findings provide insights into the role of DinJ 
      in modulating the inflammasome response during S. Enteritidis infection, 
      highlighting its impact on inhibiting inflammasome activation and immune evasion.
FAU - Gu, Dan
AU  - Gu D
AUID- ORCID: 0000-0001-6833-5358
AD  - Jiangsu Key Laboratory of Zoonosis/Jiangsu Co-innovation Center for Prevention 
      and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 
      University, Yangzhou, Jiangsu, 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, Jiangsu, China.
AD  - Joint International Research Laboratory of Agriculture and Agri-product Safety of 
      the Ministry of Education, Yangzhou University, Yangzhou, Jiangsu, China.
FAU - Li, Ang
AU  - Li A
AD  - Jiangsu Key Laboratory of Zoonosis/Jiangsu Co-innovation Center for Prevention 
      and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 
      University, Yangzhou, Jiangsu, 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, Jiangsu, China.
AD  - Joint International Research Laboratory of Agriculture and Agri-product Safety of 
      the Ministry of Education, Yangzhou University, Yangzhou, Jiangsu, China.
FAU - Zang, Xirui
AU  - Zang X
AD  - Jiangsu Key Laboratory of Zoonosis/Jiangsu Co-innovation Center for Prevention 
      and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 
      University, Yangzhou, Jiangsu, 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, Jiangsu, China.
AD  - Joint International Research Laboratory of Agriculture and Agri-product Safety of 
      the Ministry of Education, Yangzhou University, Yangzhou, Jiangsu, China.
FAU - Huang, Tingting
AU  - Huang T
AD  - Jiangsu Key Laboratory of Zoonosis/Jiangsu Co-innovation Center for Prevention 
      and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 
      University, Yangzhou, Jiangsu, 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, Jiangsu, China.
AD  - Joint International Research Laboratory of Agriculture and Agri-product Safety of 
      the Ministry of Education, Yangzhou University, Yangzhou, Jiangsu, China.
FAU - Guo, Yaxin
AU  - Guo Y
AD  - Jiangsu Key Laboratory of Zoonosis/Jiangsu Co-innovation Center for Prevention 
      and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 
      University, Yangzhou, Jiangsu, 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, Jiangsu, China.
AD  - Joint International Research Laboratory of Agriculture and Agri-product Safety of 
      the Ministry of Education, Yangzhou University, Yangzhou, Jiangsu, China.
FAU - Jiao, Xinan
AU  - Jiao X
AUID- ORCID: 0000-0002-2214-3358
AD  - Jiangsu Key Laboratory of Zoonosis/Jiangsu Co-innovation Center for Prevention 
      and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 
      University, Yangzhou, Jiangsu, 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, Jiangsu, China.
AD  - Joint International Research Laboratory of Agriculture and Agri-product Safety of 
      the Ministry of Education, Yangzhou University, Yangzhou, Jiangsu, China.
FAU - Pan, Zhiming
AU  - Pan Z
AUID- ORCID: 0000-0002-7466-872X
AD  - Jiangsu Key Laboratory of Zoonosis/Jiangsu Co-innovation Center for Prevention 
      and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 
      University, Yangzhou, Jiangsu, 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, Jiangsu, China.
AD  - Joint International Research Laboratory of Agriculture and Agri-product Safety of 
      the Ministry of Education, Yangzhou University, Yangzhou, Jiangsu, China.
LA  - eng
GR  - 32161143011/MOST | National Natural Science Foundation of China (NSFC)/
GR  - 31972685/MOST | National Natural Science Foundation of China (NSFC)/
GR  - 31920103015/MOST | National Natural Science Foundation of China (NSFC)/
PT  - Journal Article
DEP - 20240313
PL  - United States
TA  - Infect Immun
JT  - Infection and immunity
JID - 0246127
RN  - 0 (Inflammasomes)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Antitoxins)
RN  - EC 3.4.22.36 (Caspase 1)
RN  - 0 (Interleukin-1beta)
SB  - IM
MH  - Animals
MH  - Mice
MH  - *Inflammasomes/metabolism
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
MH  - Salmonella enteritidis
MH  - *Antitoxins
MH  - Mice, Inbred C57BL
MH  - Macrophages
MH  - Caspase 1/genetics
MH  - Interleukin-1beta/genetics/metabolism
PMC - PMC11003228
OTO - NOTNLM
OT  - DinJ
OT  - NLRP3 inflammasome
OT  - Salmonella Enteritidis
OT  - immune evasion
COIS- The authors declare no conflict of interest.
EDAT- 2024/03/13 12:44
MHDA- 2024/04/10 06:42
PMCR- 2024/03/13
CRDT- 2024/03/13 09:04
PHST- 2024/04/10 06:42 [medline]
PHST- 2024/03/13 12:44 [pubmed]
PHST- 2024/03/13 09:04 [entrez]
PHST- 2024/03/13 00:00 [pmc-release]
AID - 00505-23 [pii]
AID - iai.00505-23 [pii]
AID - 10.1128/iai.00505-23 [doi]
PST - ppublish
SO  - Infect Immun. 2024 Apr 9;92(4):e0050523. doi: 10.1128/iai.00505-23. Epub 2024 Mar 
      13.