TIPE2 protein serves as a negative regulator of phagocytosis and oxidative burst during infection
TIPE2 protein serves as a negative regulator of phagocytosis and oxidative burst during infection
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DOI：
10.1073/pnas.1204525109
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发表时间：
2012-09-18
影响因子：
11.1
通讯作者：
Chen, Youhai H.
中科院分区：
文献类型：
--
作者：
Wang, Zhaojun;Fayngerts, Svetlana;Chen, Youhai H.
吞噬作用和氧化爆发是先天免疫的两个主要效应臂。尽管已知两者都被Toll样受体（TLR）和Rac GTP酶激活，但它们的强度在静止和TLR激活的细胞中如何被控制尚不清楚。我们在这里报告，TIPE2（TNFAIP8L2）作为一个先天免疫的负调节器，通过连接TLR的Rac。TLR控制TIPE2的表达水平，TIPE2又通过结合和阻断Rac GTP酶决定吞噬作用和氧化爆发的强度。因此，TIPE2敲除细胞具有增强的吞噬和杀菌活性，并且TIPE2敲除小鼠对细菌感染具有抗性。因此，TIPE2设定了吞噬作用和氧化爆发的强度，并且可以靶向有效地控制感染。
Phagocytosis and oxidative burst are two major effector arms of innate immunity. Although it is known that both are activated by Toll-like receptors (TLRs) and Rac GTPases, how their strengths are controlled in quiescent and TLR-activated cells is not clear. We report here that TIPE2 (TNFAIP8L2) serves as a negative regulator of innate immunity by linking TLRs to Rac. TLRs control the expression levels of TIPE2, which in turn dictates the strengths of phagocytosis and oxidative burst by binding to and blocking Rac GTPases. Consequently, TIPE2 knockout cells have enhanced phagocytic and bactericidal activities and TIPE2 knockout mice are resistant to bacterial infection. Thus, TIPE2 sets the strengths of phagocytosis and oxidative burst and may be targeted to effectively control infections.