Tim-3 Promotes Listeria monocytogenes Immune Evasion by Suppressing Major Histocompatibility Complex Class I
Tim-3 Promotes Listeria monocytogenes Immune Evasion by Suppressing Major Histocompatibility Complex Class I
复制标题
Tim-3 通过抑制主要组织相容性复合物 I 类促进单增李斯特菌免疫逃避
DOI：
10.1093/infdis/jiz512
复制
发表时间：
2020-03-01
影响因子：
6.4
通讯作者：
Han, Gencheng
中科院分区：
文献类型：
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作者：
Wang, Zhiding;Li, Ge;Han, Gencheng
背景：T细胞免疫球蛋白和粘蛋白3(TIM-3)是一种免疫检查点抑制物，对许多肿瘤和感染性疾病具有治疗意义。方法：本研究通过抑制STAT1-NLRC5信号转导通路，从信使核糖核酸和蛋白水平抑制巨噬细胞主要组织相容性复合体I类(MHC-I)的表达。结果：TIM-3在体外和体内均能抑制巨噬细胞MHC-I限制性的抗原提呈。巨噬细胞全身性过表达TIM-3或特异性敲除TIM-3分别显著减弱或增强L单核细胞增多性T细胞活化和感染损伤。结论：进一步明确了TIM-3促进L单核细胞免疫逃避的新机制。对这一途径的进一步研究可能会为TIM-3的生理病理作用提供新的线索，并为干预提供新的方法。
Background: T-cell immunoglobulin and mucin protein 3 (Tim-3) is an immune checkpoint inhibitor that has therapeutic implications for many tumors and infectious diseases. However, the mechanisms by which Tim-3 promotes immune evasion remain unclear.Methods: In this study, we demonstrated that Tim-3 inhibits the expression of major histocompatibility complex class I (MHC-I) in macrophages at both the messenger ribonucleic acid and protein levels by inhibiting the STAT1-NLRC5 signaling pathway.Results: As a result, MHC-I-restricted antigen presentation by macrophages was inhibited by Tim-3 both in vitro and in a Listeria monocytogenes infection model in vivo. Systemic overexpression of Tim-3 or specific knockout of Tim-3 in macrophages significantly attenuated or enhanced CD8(+) T-cell activation and infection damage in L monocytogenes-infected mice, respectively.Conclusions: Thus, we identified a new mechanism by which Tim-3 promotes L monocytogenes immune evasion. Further studies on this pathway might shed new light on the physio-pathological roles of Tim-3 and suggest new approaches for intervention.