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- W4313373834 abstract "Abstract Triggering receptors expressed on myeloid cells 2 (TREM2) inhibits inflammatory responses, but promotes macrophage-mediated bacterial clearance both in vivo and in vitro. However, the underlying mechanism remains unclear. Our study demonstrated that deficiency of TREM2 significantly enhanced four common pyogenic bacteria-induced macrophage pyroptosis, including Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumoniae and Escherichia coli. Blockage of pyroptosis by knocking out Caspase-1 or knocking down gasdermin D (GSDMD) enhanced macrophage-mediated pyogenic bacteria clearance. And treatment with Caspase-1 inhibitor relieved TREM2 deficiency-mediated suppression of pyogenic bacteria clearance. In addition, TREM2 enhanced β-catenin stability via promoting its phosphorylation at S675. Moreover, silencing of β-catenin enhanced pyroptosis and impaired Pseudomonas aeruginosa clearance, while overexpression of β-catenin inhibited pyroptosis and restored bacterial elimination in TREM2-silenced macrophages. Notably, in vitro studies suggested that TREM2/β-catenin suppressed NLRP3 and NLRC4 inflammasome activation at priming and/or assembly stage. Collectively, our study provides a novel mechanism of TREM2-mediated anti-pyogenic bacterial immunity and explores the relationship between pyroptosis and bacterial eradication." @default.
- W4313373834 created "2023-01-06" @default.
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- W4313373834 date "2020-05-01" @default.
- W4313373834 modified "2023-10-18" @default.
- W4313373834 title "TREM2/β-catenin attenuates macrophage pyroptosis to promote bacterial eradication of pyogenic bacteria" @default.
- W4313373834 doi "https://doi.org/10.4049/jimmunol.204.supp.85.17" @default.
- W4313373834 hasPublicationYear "2020" @default.
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