TIPE2 蛋白在感染过程中作为吞噬作用和氧化爆发的负调节剂。
TIPE2 protein serves as a negative regulator of phagocytosis and oxidative burst during infection.
机构信息
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
出版信息
Proc Natl Acad Sci U S A. 2012 Sep 18;109(38):15413-8. doi: 10.1073/pnas.1204525109. Epub 2012 Sep 4.
Abstract
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.
摘要
吞噬作用和氧化爆发是先天免疫的两个主要效应臂。虽然已知两者都被 Toll 样受体 (TLRs) 和 Rac GTPases 激活，但在静止和 TLR 激活的细胞中，它们的强度如何被控制尚不清楚。我们在这里报告 TIPE2（TNFAIP8L2）通过将 TLRs 与 Rac 联系起来，作为先天免疫的负调节剂。TLRs 控制 TIPE2 的表达水平，而 TIPE2 通过与 Rac GTPases 结合并阻断 Rac GTPases，反过来又决定吞噬作用和氧化爆发的强度。因此，TIPE2 设定了吞噬作用和氧化爆发的强度，TIPE2 敲除细胞具有增强的吞噬和杀菌活性，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，并且可能成为有效控制感染的靶标。
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