Tim-3 inhibits macrophage control of Listeria monocytogenes by inhibiting Nrf2
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- 英文论文题名：Tim-3 inhibits macrophage control of Listeria monocytogenes by inhibiting Nrf2
- 论文作者：Wang Zhiding ; Sun Dejun ; Chen Guojiang ; Li Ge ; Dou Shuaijie ; Wang Renxi ; Xiao He ; Hou Chunmei ; Li Yan ; Feng Jiannan ; Shen Beifen ; Han Gencheng
- 英文论文作者：Wang Zhiding ; Sun Dejun ; Chen Guojiang ; Li Ge ; Dou Shuaijie ; Wang Renxi ; Xiao He ; Hou Chunmei ; Li Yan ; Feng Jiannan ; Shen Beifen ; Han Gencheng ; Department of Biomedicine ; Institute for Regeneration Medicine ; Jilin University ; Department of Immunology ; Beijing Institute of Basic Medical Sciences
- 年：2016
- 作者机构：Department of Biomedicine,Institute for Regeneration Medicine,Jilin University;Department of Immunology,Beijing Institute of Basic Medical Sciences;
- 英文论文关键词：Tim-3 ; Nrf2 ; HO-1 ; CD36 ; Listeria monocytogenes
- 会议召开时间：2016-11-04
- 会议录名称：第十一届全国免疫学学术大会摘要汇编
- 英文会议录名称：Abstracts of 2016 CSI Congress on Immunology
- 语种：英文
- 分类号：R378
- 学会代码：IGMD
- 会议名称：第十一届全国免疫学学术大会
- 会议地点：中国安徽合肥
- 主办单位：中国免疫学会
- 学会名称：中国免疫学会
- 页数：1
- 文件大小：314k
- 原文格式：D
- 会议级别：全国
摘要
Objective: 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.Methods: In this study, we use L. monocytogenes to infect RAW264.7 cells, Tim-3-TG mouse and wild type mouse inhibited Tim-3 signal. To evaluate the macrophage phagocytosis of L. monocytogenes by FACS and CLSM. To detecte Nrf2 protein level and nuclear translocation by Western blotting and High-content screening. To detecte CD36 and HO-1 mRNA by qRT–PCR. Results: We demonstrate that Tim-3 inhibits macrophage phagocytosis of L. monocytogenes by inhibiting the 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 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. Conclusion: 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.
Objective: 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.Methods: In this study, we use L. monocytogenes to infect RAW264.7 cells, Tim-3-TG mouse and wild type mouse inhibited Tim-3 signal. To evaluate the macrophage phagocytosis of L. monocytogenes by FACS and CLSM. To detecte Nrf2 protein level and nuclear translocation by Western blotting and High-content screening. To detecte CD36 and HO-1 mRNA by qRT–PCR. Results: We demonstrate that Tim-3 inhibits macrophage phagocytosis of L. monocytogenes by inhibiting the 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 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. Conclusion: 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.
Objective: 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.Methods: In this study, we use L. monocytogenes to infect RAW264.7 cells, Tim-3-TG mouse and wild type mouse inhibited Tim-3 signal. To evaluate the macrophage phagocytosis of L. monocytogenes by FACS and CLSM. To detecte Nrf2 protein level and nuclear translocation by Western blotting and High-content screening. To detecte CD36 and HO-1 mRNA by qRT–PCR. Results: We demonstrate that Tim-3 inhibits macrophage phagocytosis of L. monocytogenes by inhibiting the 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 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. Conclusion: 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.
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