TIPE2 protein serves as a negative regulator of phagocytosis and oxidative burst during infection

被引：103

作者：

Wang, Zhaojun ^{[1
,2
]}

Fayngerts, Svetlana ^{[1
]}

Wang, Peng ^{[1
]}

Sun, Honghong ^{[1
]}

Johnson, Derek S. ^{[1
]}

Ruan, Qingguo ^{[1
]}

Guo, Wei ^{[3
]}

Chen, Youhai H. ^{[1
]}

机构：

[1] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

[2] Shanghai Jiao Tong Univ, Sch Med, Dept Microbiol & Parasitol, Shanghai 20025, Peoples R China

[3] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2012年 / 109卷 / 38期

基金：

美国国家卫生研究院;

关键词：

TOLL-LIKE RECEPTORS; BACTERICIDAL ACTIVITY; IMMUNE HOMEOSTASIS; CRYSTAL-STRUCTURE; RHO-GTPASES; ACTIVATION; FAMILY; MODULATION; EXPRESSION; TNFAIP8;

D O I：

10.1073/pnas.1204525109

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：15413 / 15418

页数：6

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