The Immune Receptor NOD1 and Kinase RIP2 Interact with Bacterial Peptidoglycan on Early Endosomes to Promote Autophagy and Inflammatory Signaling

被引：203

作者：

Irving, Aaron T. ^{[1
]}

Mimuro, Hitomi ^{[2
]}

Kufer, Thomas A. ^{[3
]}

Lo, Camden ^{[4
]}

Wheeler, Richard ^{[5
,6
]}

Turner, Lorinda J. ^{[7
]}

Thomas, Belinda J. ^{[7
,8
]}

Malosse, Christian ^{[9
]}

Gantier, Michael P. ^{[1
]}

Casillas, Linda N. ^{[10
]}

Votta, Bartholomew J. ^{[10
]}

Bertin, John ^{[10
]}

Boneca, Ivo G. ^{[5
,6
]}

Sasakawa, Chihiro ^{[11
,12
,13
]}

Philpott, Dana J. ^{[14
]}

Ferrero, Richard L. ^{[7
]}

Kaparakis-Liaskos, Maria ^{[7
]}

机构：

[1] Monash Inst Med Res, Ctr Canc Res, Clayton, Vic 3168, Australia

[2] Univ Tokyo, Inst Med Sci, Div Bacteriol, Dept Infect Dis Control,Int Res Ctr Infect Dis, Tokyo 1088639, Japan

[3] Univ Cologne, Inst Med Microbiol Immunol & Hyg, D-50931 Cologne, Germany

[4] Monash Micro Imaging, Clayton, Vic 3168, Australia

[5] Inst Pasteur, Unite Biol & Genet Paroi Bacterienne, F-75015 Paris, France

[6] INSERM, Avenir Grp, F-75015 Paris, France

[7] Monash Inst Med Res, Ctr Innate Immun & Infect Dis, Clayton, Vic 3168, Australia

[8] Monash Med Ctr, Monash Lung & Sleep, Clayton, Vic 3168, Australia

[9] Inst Pasteur, Struct Mass Spectrometry & Prote Unit, F-75015 Paris, France

[10] GlaxoSmithKline, Pattern Recognit Receptor Discovery Performance U, Immunoinflammat Therapy Area, Collegeville, PA 19426 USA

[11] Univ Tokyo, Inst Med Sci, Div Bacterial Infect Biol, Tokyo 1088639, Japan

[12] Nippon Inst Biol Sci, Tokyo 1980024, Japan

[13] Chiba Univ, Med Mycol Res Ctr, Chiba 2608673, Japan

[14] Univ Toronto, Dept Immunol, Toronto, ON M5S 1A8, Canada

来源：

CELL HOST & MICROBE | 2014年 / 15卷 / 05期

基金：

英国医学研究理事会; 澳大利亚研究理事会;

关键词：

NF-KAPPA-B; OUTER-MEMBRANE VESICLES; HELICOBACTER-PYLORI; ACTIVATION; RECOGNITION; MOLECULE; CELL;

D O I：

10.1016/j.chom.2014.04.001

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

The intracellular innate immune receptor NOD1 detects Gram-negative bacterial peptidoglycan (PG) to induce autophagy and inflammatory responses in host cells. To date, the intracellular compartment in which PG is detected by NOD1 and whether NOD1 directly interacts with PG are two questions that remain to be resolved. To address this, we used outer membrane vesicles (OMVs) from pathogenic bacteria as a physiological mechanism to deliver PG into the host cell cytosol. We report that OMVs induced autophagosome formation and inflammatory IL-8 responses in epithelial cells in a NOD1-and RIP2-dependent manner. PG contained within OMVs colocalized with both NOD1 and RIP2 in EEA1-positive early endosomes. Further, we provide evidence for direct interactions between NOD1 and PG. Collectively, these findings demonstrate that NOD1 detects PG within early endosomes, thereby promoting RIP2-dependent autophagy and inflammatory signaling in response to bacterial infection.

引用

页码：623 / 635

页数：13

共 21 条

[21] NOD/RIP2 signaling in response to non-peptidoglycan containing pathogen contribute to development of a TH1-biased response and resistance against L. major infection
Lima-Junior, D. S.
Silva, J. S.
Zamboni, D. S.
[J]. EUROPEAN JOURNAL OF IMMUNOLOGY, 2016, 46 : 1030 - 1030

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