O<sup>6</sup>-methylguanine DNA methyltransferase regulates β-glucan-induced trained immunity of macrophages via farnesoid X receptor and AMPK
Issued Date
2024-01-19
Resource Type
eISSN
25890042
Scopus ID
2-s2.0-85181125220
Journal Title
iScience
Volume
27
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
iScience Vol.27 No.1 (2024)
Suggested Citation
Benjaskulluecha S., Boonmee A., Haque M.F., Wongprom B., Pattarakankul T., Pongma C., Sri-ngern-ngam K., Keawvilai P., Sukdee T., Saechue B., Kueanjinda P., Palaga T. O<sup>6</sup>-methylguanine DNA methyltransferase regulates β-glucan-induced trained immunity of macrophages via farnesoid X receptor and AMPK. iScience Vol.27 No.1 (2024). doi:10.1016/j.isci.2023.108733 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/95915
Title
O<sup>6</sup>-methylguanine DNA methyltransferase regulates β-glucan-induced trained immunity of macrophages via farnesoid X receptor and AMPK
Corresponding Author(s)
Other Contributor(s)
Abstract
Trained immunity is the heightened state of innate immune memory that enhances immune response resulting in nonspecific protection. Epigenetic changes and metabolic reprogramming are critical steps that regulate trained immunity. In this study, we reported the involvement of O6-methylguanine DNA methyltransferase (MGMT), a DNA repair enzyme of lesion induced by alkylating agents, in regulation the trained immunity induced by β-glucan (BG). Pharmacological inhibition or silencing of MGMT expression altered LPS stimulated pro-inflammatory cytokine productions in BG-trained bone marrow derived macrophages (BMMs). Targeted deletion of Mgmt in BMMs resulted in reduction of the trained responses both in vitro and in vivo models. The transcriptomic analysis revealed that the dampening trained immunity in MGMT KO BMMs is partially mediated by ATM/FXR/AMPK axis affecting the MAPK/mTOR/HIF1α pathways and the reduction in glycolysis function. Taken together, a failure to resolve a DNA damage may have consequences for innate immune memory.