| First Author | Wang C | Year | 2018 |
| Journal | Immunity | Volume | 48 |
| Issue | 4 | Pages | 675-687.e7 |
| PubMed ID | 29653696 | Mgi Jnum | J:272659 |
| Mgi Id | MGI:6284454 | Doi | 10.1016/j.immuni.2018.03.017 |
| Citation | Wang C, et al. (2018) Manganese Increases the Sensitivity of the cGAS-STING Pathway for Double-Stranded DNA and Is Required for the Host Defense against DNA Viruses. Immunity 48(4):675-687.e7 |
| abstractText | Manganese (Mn) is essential for many physiological processes, but its functions in innate immunity remain undefined. Here, we found that Mn(2+) was required for the host defense against DNA viruses by increasing the sensitivity of the DNA sensor cGAS and its downstream adaptor protein STING. Mn(2+) was released from membrane-enclosed organelles upon viral infection and accumulated in the cytosol where it bound directly to cGAS. Mn(2+) enhanced the sensitivity of cGAS to double-stranded DNA (dsDNA) and its enzymatic activity, enabling cGAS to produce secondary messenger cGAMP in the presence of low concentrations of dsDNA that would otherwise be non-stimulatory. Mn(2+) also enhanced STING activity by augmenting cGAMP-STING binding affinity. Mn-deficient mice showed diminished cytokine production and were more vulnerable to DNA viruses, and Mn-deficient STING-deficient mice showed no increased susceptibility. These findings indicate that Mn is critically involved and required for the host defense against DNA viruses. |
