PMID- 33848212
OWN - NLM
STAT- MEDLINE
DCOM- 20210913
LR  - 20210913
IS  - 1535-4989 (Electronic)
IS  - 1044-1549 (Linking)
VI  - 65
IP  - 2
DP  - 2021 Aug
TI  - TREM2 Dictates Antibacterial Defense and Viability of Bone Marrow-derived 
      Macrophages during Bacterial Infection.
PG  - 176-188
LID - 10.1165/rcmb.2020-0521OC [doi]
AB  - Macrophages undergo profound metabolic reprogramming to join key immunoregulatory 
      functions, which can be initiated by pattern recognition receptors. TREM2 
      (triggering receptor expressed on myeloid cells 2), a macrophage phagocytic 
      receptor, plays pivotal roles in sepsis by enhancing bacterial clearance, which 
      is associated with regulation of reactive oxygen species (ROS) production. 
      However, how intracellular ROS participate in TREM2-mediated bactericidal 
      activity remains unclear. This study was designed to investigate the organelle 
      source and biological activity of ROS in the context of TREM2-mediated immune 
      defense during Escherichiacoli infection. Bone marrow-derived macrophages (BMDMs) 
      were transfected with TREM2-overexpressing adenoviruses or control viruses and 
      challenged with E. coli. The BMDMs were administered to mouse models with local 
      E. coli infection. In addition, monocytic TREM2 expression, NOX2 concentrations, 
      and pyroptosis were detected in patients with bacterial sepsis. General ROS 
      production was found to be comparable between TREM2-overexpressing and control 
      BMDMs upon E. coli challenge. The deficiency of Nox2 led to impaired phagosome 
      degradation and lack of bactericidal ability and abolished TREM2-mediated 
      protective activity against pulmonary E. coli infection. Overexpression of TREM2 
      suppressed mitochondrial ROS generation, inhibited NLRP3/caspase-1 inflammasome 
      activation, and finally protected BMDMs from gasdermin D-mediated pyroptosis 
      during pulmonary E. coli infection. The protective role of TREM2 was further 
      confirmed in mice with abdominal E. coli infection. Moreover, monocytic TREM2 
      expression was positively correlated with NOX2 concentrations and negatively 
      correlated with pyroptosis and disease severity in patients with bacterial 
      sepsis. Collectively, TREM2 controls macrophage immune functions by fine-tuning 
      ROS generation and enhances the host defense against bacterial infection. Our 
      data suggest that TREM2 is a promising candidate target for sepsis therapy.
FAU - Yang, ShiYue
AU  - Yang S
AD  - Department of Anesthesiology and Intensive Care, The First Affiliated Hospital, 
      School of Medicine, Zhejiang University, Hangzhou, China; and.
FAU - Yang, Yang
AU  - Yang Y
AD  - Department of Anesthesiology and Intensive Care, The First Affiliated Hospital, 
      School of Medicine, Zhejiang University, Hangzhou, China; and.
FAU - Wang, FeiFei
AU  - Wang F
AD  - Department of Anesthesiology and Intensive Care, The First Affiliated Hospital, 
      School of Medicine, Zhejiang University, Hangzhou, China; and.
FAU - Luo, QinYu
AU  - Luo Q
AD  - Department of Clinical Research Center, The Children's Hospital, School of 
      Medicine, Zhejiang University, National Clinical Research Center for Child 
      Health, Hangzhou, China.
FAU - Zhang, Yan
AU  - Zhang Y
AD  - Department of Clinical Research Center, The Children's Hospital, School of 
      Medicine, Zhejiang University, National Clinical Research Center for Child 
      Health, Hangzhou, China.
FAU - Zheng, Fei
AU  - Zheng F
AD  - Department of Clinical Research Center, The Children's Hospital, School of 
      Medicine, Zhejiang University, National Clinical Research Center for Child 
      Health, Hangzhou, China.
FAU - Shu, Qiang
AU  - Shu Q
AD  - Department of Clinical Research Center, The Children's Hospital, School of 
      Medicine, Zhejiang University, National Clinical Research Center for Child 
      Health, Hangzhou, China.
FAU - Chen, QiXing
AU  - Chen Q
AD  - Department of Clinical Research Center, The Children's Hospital, School of 
      Medicine, Zhejiang University, National Clinical Research Center for Child 
      Health, Hangzhou, China.
FAU - Fang, XiangMing
AU  - Fang X
AD  - Department of Anesthesiology and Intensive Care, The First Affiliated Hospital, 
      School of Medicine, Zhejiang University, Hangzhou, China; and.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Respir Cell Mol Biol
JT  - American journal of respiratory cell and molecular biology
JID - 8917225
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Trem2 protein, mouse)
RN  - EC 1.6.3.- (Cybb protein, mouse)
RN  - EC 1.6.3.- (NADPH Oxidase 2)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/*immunology/pathology
MH  - Escherichia coli/*immunology
MH  - Escherichia coli Infections/genetics/*immunology
MH  - Gene Expression Regulation/immunology
MH  - Macrophages/*immunology/pathology
MH  - Membrane Glycoproteins/genetics/*immunology
MH  - Mice
MH  - Mice, Knockout
MH  - NADPH Oxidase 2/genetics/immunology
MH  - Phagosomes/genetics/immunology
MH  - Pneumonia, Bacterial/genetics/*immunology/pathology
MH  - Receptors, Immunologic/genetics/*immunology
OTO - NOTNLM
OT  - NOX2
OT  - TREM2
OT  - mitochondria
OT  - pyroptosis
OT  - sepsis
EDAT- 2021/04/14 06:00
MHDA- 2021/09/14 06:00
CRDT- 2021/04/13 17:10
PHST- 2021/04/14 06:00 [pubmed]
PHST- 2021/09/14 06:00 [medline]
PHST- 2021/04/13 17:10 [entrez]
AID - 10.1165/rcmb.2020-0521OC [doi]
PST - ppublish
SO  - Am J Respir Cell Mol Biol. 2021 Aug;65(2):176-188. doi: 10.1165/rcmb.2020-0521OC.