Tim-3 inhibits macrophage control of Listeria monocytogenes by inhibiting Nrf2

• DOI: 10.1038/srep42095
• Publication Date: 2017-02-16T10:23:53Z
• Authors: Zhiding Wang; Dejun Sun; Guojiang Chen; Ge Li; Shuaijie Dou; Renxi Wang; He Xiao; Chunmei Hou; Yan Li; Jiannan Feng; Beifen Shen; Gencheng Han
• Keywords: CD36 Antigens; 0301 basic medicine; 0303 health sciences; NF-E2-Related Factor 2; Macrophages; Listeria monocytogenes; Article; 3. Good health; Mice, Inbred C57BL; Mice; 03 medical and health sciences; HEK293 Cells; RAW 264.7 Cells; Phagocytosis; Animals; Humans; Hepatitis A Virus Cellular Receptor 2; Heme Oxygenase-1; Immune Evasion; Signal Transduction

Abstract T cell immunoglobulin mucin-3 (Tim-3) is an immune checkpoint inhibitor and its dysregulation has been related to tolerance many disorders, such as tumors infection tolerance. However, the physiopathology roles of Tim-3 in innate immunity remain elusive. Here, we demonstrate that inhibits macrophage phagocytosis L. monocytogenes by inhibiting nuclear erythroid 2-related factor 2 (Nrf2) signaling pathway increases bacterial burden. promotes Nrf2 degradation increasing ubiquitination and, a result, decreasing translocation. CD36 heme oxygenase-1 (HO-1), two downstream molecules Tim-3-Nrf2 axis, are involved Tim-3- mediated evasion both vitro vivo . We here identified new mechanisms which induces By modulating pathway, feasibility manipulating function potent tool for treating infectious diseases, Listeria infection.