PMID- 32205422
OWN - NLM
STAT- MEDLINE
DCOM- 20210216
LR  - 20240214
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 204
IP  - 9
DP  - 2020 May 1
TI  - IRF8 Regulates Gram-Negative Bacteria-Mediated NLRP3 Inflammasome Activation and 
      Cell Death.
PG  - 2514-2522
LID - 10.4049/jimmunol.1901508 [doi]
AB  - Inflammasomes are intracellular signaling complexes that are assembled in 
      response to a variety of pathogenic or physiologic stimuli to initiate 
      inflammatory responses. Ubiquitously present LPS in Gram-negative bacteria 
      induces NLRP3 inflammasome activation that requires caspase-11. We have recently 
      demonstrated that IFN regulatory factor (IRF) 8 was dispensable for 
      caspase-11-mediated NLRP3 inflammasome activation during LPS transfection; 
      however, its role in Gram-negative bacteria-mediated NLRP3 inflammasome 
      activation remains unknown. In this study, we found that IRF8 promotes NLRP3 
      inflammasome activation in murine bone marrow-derived macrophages (BMDMs) 
      infected with Gram-negative bacteria such as Citrobacter rodentium, Escherichia 
      coli, or Pseudomonas aeruginosa mutant strain DeltapopB Moreover, BMDMs deficient in 
      IRF8 showed substantially reduced caspase-11 activation and gasdermin D cleavage, 
      which are required for NLRP3 inflammasome activation. Mechanistically, 
      IRF8-mediated phosphorylation of IRF3 was required for Ifnb transcription, which 
      in turn triggered the caspase-11-dependent NLRP3 inflammasome activation in the 
      infected BMDMs. Overall, our findings suggest that IRF8 promotes NLRP3 
      inflammasome activation during infection with Gram-negative bacteria.
CI  - Copyright (c) 2020 by The American Association of Immunologists, Inc.
FAU - Karki, Rajendra
AU  - Karki R
AD  - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 
      38105; and.
FAU - Lee, Ein
AU  - Lee E
AD  - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 
      38105; and.
AD  - Integrated Biomedical Sciences Program, University of Tennessee Health Science 
      Center, Memphis, TN 38163.
FAU - Sharma, Bhesh R
AU  - Sharma BR
AUID- ORCID: 0000-0003-3609-833X
AD  - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 
      38105; and.
FAU - Banoth, Balaji
AU  - Banoth B
AD  - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 
      38105; and.
FAU - Kanneganti, Thirumala-Devi
AU  - Kanneganti TD
AUID- ORCID: 0000-0002-6395-6443
AD  - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 
      38105; and Thirumala-Devi.Kanneganti@StJude.org.
LA  - eng
GR  - R01 AI101935/AI/NIAID NIH HHS/United States
GR  - R01 AI124346/AI/NIAID NIH HHS/United States
GR  - R01 CA163507/CA/NCI NIH HHS/United States
GR  - R37 AI101935/AI/NIAID NIH HHS/United States
GR  - R01 AR056296/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20200323
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Inflammasomes)
RN  - 0 (Interferon Regulatory Factors)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Nlrp3 protein, mouse)
RN  - 0 (interferon regulatory factor-8)
RN  - EC 3.4.22.- (Caspases, Initiator)
SB  - IM
MH  - Animals
MH  - Caspases, Initiator/metabolism
MH  - Cell Death/*physiology
MH  - Cells, Cultured
MH  - Female
MH  - Gram-Negative Bacteria/*pathogenicity
MH  - Gram-Negative Bacterial Infections/*metabolism/microbiology
MH  - Inflammasomes/*metabolism
MH  - Interferon Regulatory Factors/*metabolism
MH  - Macrophages/metabolism/microbiology
MH  - Male
MH  - Mice
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/*metabolism
MH  - Signal Transduction/physiology
PMC - PMC7291389
MID - NIHMS1590189
COIS- COMPETING FINANCIAL INTERESTS The authors declare no competing financial 
      interests.
EDAT- 2020/03/25 06:00
MHDA- 2021/02/17 06:00
PMCR- 2020/11/01
CRDT- 2020/03/25 06:00
PHST- 2019/12/20 00:00 [received]
PHST- 2020/02/24 00:00 [accepted]
PHST- 2020/03/25 06:00 [pubmed]
PHST- 2021/02/17 06:00 [medline]
PHST- 2020/03/25 06:00 [entrez]
PHST- 2020/11/01 00:00 [pmc-release]
AID - jimmunol.1901508 [pii]
AID - 10.4049/jimmunol.1901508 [doi]
PST - ppublish
SO  - J Immunol. 2020 May 1;204(9):2514-2522. doi: 10.4049/jimmunol.1901508. Epub 2020 
      Mar 23.