Host sirtuin 1 regulates mycobacterial immunopathogenesis and represents a therapeutic target against tuberculosis

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Science Immunology  24 Mar 2017:
Vol. 2, Issue 9, eaaj1789
DOI: 10.1126/sciimmunol.aaj1789

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Mtb faces sirtuin death

Mycobacterium tuberculosis (Mtb) is the poster child for drug resistance, and new therapies are needed to combat this reemerging infection. Now, Cheng et al. report that Mtb infection down-regulates sirtuin 1, a NAD+-dependent deacetylase, in myeloid cells in animal models and patients with active disease. Activating sirtuin 1 inhibited intracellular growth of Mtb and persistent inflammatory responses, decreasing lung pathology. Sirtuin 1 activation also enhanced the efficacy of a first-line antituberculosis drug. These effects may be due, in part, to myeloid cell modulation, because mice with myeloid cell–specific SIRT1 deficiency had both increased inflammation and higher susceptibility to infection than wild-type controls. Thus, sirtuin 1 may be a target for host-directed therapy for Mtb.