PMID- 35399524
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220413
IS  - 2296-634X (Print)
IS  - 2296-634X (Electronic)
IS  - 2296-634X (Linking)
VI  - 10
DP  - 2022
TI  - Stimulator of Interferon Genes (STING) Promotes Staphylococcus aureus-Induced 
      Extracellular Traps Formation via the ROS-ERK Signaling Pathway.
PG  - 836880
LID - 10.3389/fcell.2022.836880 [doi]
LID - 836880
AB  - Stimulator of interferon genes (STING) is a cytosolic DNA sensor or directly 
      recognizes bacterial cyclic dinucleotides, which is required for the detection of 
      microbial infection. Extracellular traps (ETs) are known to be part of the 
      antimicrobial defense system. However, the implication of STING in ETs formation 
      during microbial infection remains unknown. Here, we showed that STING 
      contributed to Staphylococcus aureus (S. aureus)-induced ETs formation through 
      the ROS-ERK signaling. STING deficiency exhibited decreased cell-free DNA (cfDNA) 
      level, reduced expression of citrullinated histone H3 (CitH3), and diminished DNA 
      colocalization with CitH3 and myeloperoxidase (MPO). Interestingly, NADPH 
      oxidase-derived reactive oxygen species (ROS) promoted ETs formation, accompanied 
      by increased activation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) 
      in S. aureus-stimulated bone marrow-derived macrophages (BMDMs). Corresponding to 
      less ROS production, decreased ERK1/2 activation was shown in STING(-/-) BMDMs 
      after S. aureus infection. Importantly, inhibiting the ROS-ERK signal reduced the 
      ETs formation and the differences disappeared between WT and STING(-/-) BMDMs 
      after S. aureus infection. Moreover, STING(-/-) BMDMs exhibited significantly 
      increased levels of extracellular bacteria compared to WT BMDMs regardless of 
      phagocytosis. In addition, such differences disappeared after DNase I treatment. 
      DNase I treatment also facilitated pathogen colonization without affecting the 
      inflammatory cells infiltration and pro-inflammatory factors secretion following 
      pulmonary S. aureus infection. Furthermore, STING(-/-) mice presented decreased 
      levels of cfDNA and CitH3, along with increased bacterial colonization compared 
      to WT mice. Altogether, these findings highlighted that STING promoted ETs 
      formation via the ROS-ERK signal for host defense against S. aureus infection.
CI  - Copyright (c) 2022 Liu, Chen, Zhou, Ma, Gao and Yang.
FAU - Liu, Zhen-Zhen
AU  - Liu ZZ
AD  - Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary 
      Medicine, Jilin University, Changchun, China.
FAU - Chen, Wei
AU  - Chen W
AD  - Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary 
      Medicine, Jilin University, Changchun, China.
FAU - Zhou, Cheng-Kai
AU  - Zhou CK
AD  - Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary 
      Medicine, Jilin University, Changchun, China.
FAU - Ma, Ke
AU  - Ma K
AD  - Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary 
      Medicine, Jilin University, Changchun, China.
FAU - Gao, Yu
AU  - Gao Y
AD  - Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary 
      Medicine, Jilin University, Changchun, China.
FAU - Yang, Yong-Jun
AU  - Yang YJ
AD  - Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary 
      Medicine, Jilin University, Changchun, China.
LA  - eng
PT  - Journal Article
DEP - 20220323
PL  - Switzerland
TA  - Front Cell Dev Biol
JT  - Frontiers in cell and developmental biology
JID - 101630250
PMC - PMC8984202
OTO - NOTNLM
OT  - NADPH oxidase
OT  - STING
OT  - Staphylococcus aureus
OT  - extracellular traps
OT  - innate immune
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/04/12 06:00
MHDA- 2022/04/12 06:01
PMCR- 2022/01/01
CRDT- 2022/04/11 05:14
PHST- 2021/12/16 00:00 [received]
PHST- 2022/01/28 00:00 [accepted]
PHST- 2022/04/11 05:14 [entrez]
PHST- 2022/04/12 06:00 [pubmed]
PHST- 2022/04/12 06:01 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 836880 [pii]
AID - 10.3389/fcell.2022.836880 [doi]
PST - epublish
SO  - Front Cell Dev Biol. 2022 Mar 23;10:836880. doi: 10.3389/fcell.2022.836880. 
      eCollection 2022.