Alleviation of monocyte exhaustion by BCG derivative mycolic acid
| dc.contributor.author | Wu, Yajun | en |
| dc.contributor.author | Caldwell, Blake | en |
| dc.contributor.author | Wang, Jing | en |
| dc.contributor.author | Zhang, Yao | en |
| dc.contributor.author | Li, Liwu | en |
| dc.date.accessioned | 2024-02-01T13:51:01Z | en |
| dc.date.available | 2024-02-01T13:51:01Z | en |
| dc.date.issued | 2024-01 | en |
| dc.description.abstract | Monocyte exhaustion with sustained pathogenic inflammation and immune-suppression, a hallmark of sepsis resulting from systemic infections, presents a challenge with limited therapeutic solutions. This study identified Methoxy-Mycolic Acid (M-MA), a branchedmycolic acid derived from Mycobacterium bovis Bacillus Calmette–Gue´ rin (BCG), as a potent agent in alleviating monocyte exhaustion and restoring immune homeostasis. Co-treatment of monocytes with M-MA effectively blocked the expansion of Ly6Chi/CD38hi/PD-L1hi monocytes induced by LPS challenges and restored the expression of immuneenhancing CD86. M-MA treatment restored mitochondrial functions of exhausted monocytes and alleviated their suppressive activities on co-cultured T cells. Independent of TREM2, M-MA blocks Src-STAT1- mediated inflammatory polarization and reduces the production of immune suppressors TAX1BP1 and PLAC8. Whole genome methylation analyses revealed M-MA’s ability to erase the methylation memory of exhausted monocytes, particularly restoring Plac8 methylation. Together, our data suggest M-MA as an effective agent in restoring monocyte homeostasis with a therapeutic potential for treating sepsis. | en |
| dc.description.version | Published version | en |
| dc.format.mimetype | application/pdf | en |
| dc.identifier | 108978 (Article number) | en |
| dc.identifier.doi | https://doi.org/10.1016/j.isci.2024.108978 | en |
| dc.identifier.issn | 2589-0042 | en |
| dc.identifier.orcid | Li, Liwu [0000-0001-8870-5299] | en |
| dc.identifier.uri | https://hdl.handle.net/10919/117775 | en |
| dc.language.iso | en | en |
| dc.publisher | Elsevier | en |
| dc.rights | Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International | en |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | en |
| dc.title | Alleviation of monocyte exhaustion by BCG derivative mycolic acid | en |
| dc.title.serial | iScience | en |
| dc.type | Article - Refereed | en |
| dc.type.dcmitype | Text | en |
| pubs.organisational-group | /Virginia Tech | en |
| pubs.organisational-group | /Virginia Tech/Science | en |
| pubs.organisational-group | /Virginia Tech/Science/Biological Sciences | en |
| pubs.organisational-group | /Virginia Tech/Faculty of Health Sciences | en |
| pubs.organisational-group | /Virginia Tech/All T&R Faculty | en |
| pubs.organisational-group | /Virginia Tech/Science/COS T&R Faculty | en |
| pubs.organisational-group | /Virginia Tech/VT Carilion School of Medicine | en |
| pubs.organisational-group | /Virginia Tech/VT Carilion School of Medicine/Internal Medicine | en |
| pubs.organisational-group | /Virginia Tech/VT Carilion School of Medicine/Internal Medicine/Secondary Appointment- Internal Medicine | en |
| pubs.organisational-group | /Virginia Tech/VT Carilion School of Medicine/Internal Medicine/Internal Med-Subgroup | en |