First Author | Heinonen T | Year | 2019 |
Journal | Front Immunol | Volume | 10 |
Pages | 2341 | PubMed ID | 31632409 |
Mgi Jnum | J:284390 | Mgi Id | MGI:6381008 |
Doi | 10.3389/fimmu.2019.02341 | Citation | Heinonen T, et al. (2019) Impact of the Dual Deletion of the Mitochondrial Sirtuins SIRT3 and SIRT5 on Anti-microbial Host Defenses. Front Immunol 10:2341 |
abstractText | The sirtuins SIRT3 and SIRT5 are the main mitochondrial lysine deacetylase and desuccinylase, respectively. SIRT3 and SIRT5 regulate metabolism and redox homeostasis and have been involved in age-associated metabolic, neurologic and oncologic diseases. We have previously shown that single deficiency in either SIRT3 or SIRT5 had no impact on host defenses in a large panel of preclinical models of sepsis. However, SIRT3 and SIRT5 may compensate each other considering that they share subcellular location and targets. Here, we generated a SIRT3/5 double knockout mouse line. SIRT3/5 deficient mice multiplied and developed without abnormalities. Hematopoiesis and immune cell development were largely unaffected in SIRT3/5 deficient mice. Whole blood, macrophages and neutrophils from SIRT3/5 deficient mice displayed enhanced inflammatory and bactericidal responses. In agreement, SIRT3/5 deficient mice showed somewhat improved resistance to Listeria monocytogenes infection. Overall, the double deficiency in SIRT3 and SIRT5 has rather subtle impacts on immune cell development and anti-microbial host defenses unseen in single deficient mice, indicating a certain degree of overlap between SIRT3 and SIRT5. These data support the assumption that therapies directed against mitochondrial sirtuins, at least SIRT3 and SIRT5, should not impair antibacterial host defenses. |