| First Author | Bhaskar A | Year | 2020 |
| Journal | Elife | Volume | 9 |
| PubMed ID | 32697192 | Mgi Jnum | J:351668 |
| Mgi Id | MGI:6450829 | Doi | 10.7554/eLife.55415 |
| Citation | Bhaskar A, et al. (2020) Host sirtuin 2 as an immunotherapeutic target against tuberculosis. Elife 9 |
| abstractText | Mycobacterium tuberculosis (Mtb) employs plethora of mechanisms to hijack the host defence machinery for its successful survival, proliferation and persistence. Here, we show that Mtb upregulates one of the key epigenetic modulators, NAD+ dependent histone deacetylase Sirtuin 2 (SIRT2), which upon infection translocate to the nucleus and deacetylates histone H3K18, thus modulating the host transcriptome leading to enhanced macrophage activation. Furthermore, in Mtb specific T cells, SIRT2 deacetylates NFkappaB-p65 at K310 to modulate T helper cell differentiation. Pharmacological inhibition of SIRT2 restricts the intracellular growth of both drug-sensitive and resistant strains of Mtb and enhances the efficacy of front line anti-TB drug Isoniazid in the murine model of infection. SIRT2 inhibitor-treated mice display reduced bacillary load, decreased disease pathology and increased Mtb-specific protective immune responses. Overall, this study provides a link between Mtb infection, epigenetics and host immune response, which can be exploited to achieve therapeutic benefits. |
