Alleviation of monocyte exhaustion by BCG derivative mycolic acid
Summary: 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 branched mycolic acid derived from Mycoba...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-02-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224001998 |
| _version_ | 1797336910648049664 |
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| author | Yajun Wu Blake Caldwell Jing Wang Yao Zhang Liwu Li |
| author_facet | Yajun Wu Blake Caldwell Jing Wang Yao Zhang Liwu Li |
| author_sort | Yajun Wu |
| collection | DOAJ |
| description | Summary: 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 branched mycolic acid derived from Mycobacterium bovis Bacillus Calmette–Guérin (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 immune-enhancing 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. |
| first_indexed | 2024-03-08T09:01:46Z |
| format | Article |
| id | doaj.art-ad4b6a9bbce244948c7af678ea482b52 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-08T09:01:46Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-ad4b6a9bbce244948c7af678ea482b522024-02-01T06:35:02ZengElsevieriScience2589-00422024-02-01272108978Alleviation of monocyte exhaustion by BCG derivative mycolic acidYajun Wu0Blake Caldwell1Jing Wang2Yao Zhang3Liwu Li4Department of Biological Sciences, Virginia Tech; Blacksburg, VA 24061-0910, USADepartment of Biological Sciences, Virginia Tech; Blacksburg, VA 24061-0910, USADepartment of Biological Sciences, Virginia Tech; Blacksburg, VA 24061-0910, USADepartment of Biological Sciences, Virginia Tech; Blacksburg, VA 24061-0910, USADepartment of Biological Sciences, Virginia Tech; Blacksburg, VA 24061-0910, USA; Corresponding authorSummary: 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 branched mycolic acid derived from Mycobacterium bovis Bacillus Calmette–Guérin (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 immune-enhancing 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.http://www.sciencedirect.com/science/article/pii/S2589004224001998EpigeneticsImmunologyMolecular biology |
| spellingShingle | Yajun Wu Blake Caldwell Jing Wang Yao Zhang Liwu Li Alleviation of monocyte exhaustion by BCG derivative mycolic acid iScience Epigenetics Immunology Molecular biology |
| title | Alleviation of monocyte exhaustion by BCG derivative mycolic acid |
| title_full | Alleviation of monocyte exhaustion by BCG derivative mycolic acid |
| title_fullStr | Alleviation of monocyte exhaustion by BCG derivative mycolic acid |
| title_full_unstemmed | Alleviation of monocyte exhaustion by BCG derivative mycolic acid |
| title_short | Alleviation of monocyte exhaustion by BCG derivative mycolic acid |
| title_sort | alleviation of monocyte exhaustion by bcg derivative mycolic acid |
| topic | Epigenetics Immunology Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224001998 |
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