| First Author | Wang Z | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Pages | 42095 | PubMed ID | 28205579 |
| Mgi Jnum | J:275074 | Mgi Id | MGI:6296073 |
| Doi | 10.1038/srep42095 | Citation | Wang Z, et al. (2017) Tim-3 inhibits macrophage control of Listeria monocytogenes by inhibiting Nrf2. Sci Rep 7:42095 |
| abstractText | T cell immunoglobulin mucin-3 (Tim-3) is an immune checkpoint inhibitor and its dysregulation has been related to T cell tolerance and many immune disorders, such as tumors and infection tolerance. However, the physiopathology roles of Tim-3 in innate immunity remain elusive. Here, we demonstrate that Tim-3 inhibits macrophage phagocytosis of L. monocytogenes by inhibiting the nuclear erythroid 2-related factor 2 (Nrf2) signaling pathway and increases bacterial burden. Tim-3 signaling promotes Nrf2 degradation by increasing its ubiquitination and, as a result, decreasing its nuclear translocation. CD36 and heme oxygenase-1 (HO-1), two downstream molecules in the Tim-3-Nrf2 signaling axis, are involved in the Tim-3- mediated immune evasion of L. monocytogenes both in vitro and in vivo. We here identified new mechanisms by which Tim-3 induces infection tolerance. By modulating the Tim-3 pathway, we demonstrate the feasibility of manipulating macrophage function as a potent tool for treating infectious diseases, such as Listeria infection. |
