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TREM‐2 Promotes Macrophage‐Mediated Eradication of Pseudomonas aeruginosa via a PI3K/Akt Pathway
Author(s) -
Zhu M.,
Li D.,
Wu Y.,
Huang X.,
Wu M.
Publication year - 2014
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/sji.12148
Subject(s) - wortmannin , pi3k/akt/mtor pathway , protein kinase b , macrophage , microbiology and biotechnology , p38 mitogen activated protein kinases , mapk/erk pathway , intracellular , biology , reactive oxygen species , chemistry , signal transduction , biochemistry , in vitro
Triggering receptor expressed on myeloid cells 2 ( TREM ‐2) is a cell surface receptor abundantly expressed on myeloid lineage cells such as macrophages and dendritic cells. It is reported that TREM ‐2 functions as an inflammatory inhibitor in macrophages and dendritic cells. However, the role of TREM ‐2 in bacterial killing remains unclear. This study explored the role of TREM ‐2 in bacterial eradication of Pseudomonas aeruginosa ( PA ), a Gram‐negative bacterium which causes various opportunistic infections. Phagocytosis assay assessed by flow cytometry suggested that TREM‐2 was not involved in the uptake of PA by macrophages, while bacterial plate count data showed that TREM‐2 was required for macrophage‐mediated intracellular killing of PA. Moreover, our results demonstrated that TREM‐2 promoted macrophage killing by enhancing reactive oxygen species (ROS), but not nitric oxygen (NO) production. Treatment with N‐acetylcysteine, a ROS scavenger, diminished the TREM‐2‐mediated intracellular killing of PA. To further investigate the underlined mechanisms of TREM‐2‐promoted bacterial killing, we examined the activation of downstream mitogen‐activated protein kinases and PI3K/Akt pathway. Western blot data showed that silencing of TREM‐2 inhibited phosphorylation of Akt, but not ERK, JNK or P38. In addition, pretreatment with PI3K active product PIP3 DiC16 reversed the elevation of intracellular bacterial load in TREM‐2‐silenced macrophages, while PI3K inhibitor wortmannin restored the decline of bacterial load in TREM‐2‐overexpressed macrophages. These data together suggested that the TREM‐2‐mediated bacterial killing is dependent on the activation of PI3K/Akt signalling, which may provide a better understanding of the host antibacterial immune defence.