Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry

被引：1007

作者：

Travassos, Leonardo H. ^{[1
]}

Carneiro, Leticia A. M. ^{[2
]}

Ramjeet, Mahendrasingh ^{[2
]}

Hussey, Seamus ^{[1
,3
]}

Kim, Yun-Gi ^{[4
]}

Magalhaes, Joao G. ^{[1
]}

Yuan, Linda ^{[1
]}

Soares, Fraser ^{[2
]}

Chea, Evelyn ^{[1
]}

Le Bourhis, Lionel ^{[1
]}

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

Allaoui, Abdelmounaaim ^{[7
]}

Jones, Nicola L. ^{[3
]}

Nunez, Gabriel ^{[4
]}

Girardin, Stephen E. ^{[2
]}

Philpott, Dana J. ^{[1
]}

机构：

[1] Univ Toronto, Dept Immunol, Toronto, ON, Canada

[2] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada

[3] Hosp Sick Children, Toronto, ON M5G 1X8, Canada

[4] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA

[5] Inst Pasteur, Biol & Genet Bacterial Cell Wall Grp, Paris, France

[6] INSERM, Avenir Grp, Paris, France

[7] Univ Libre Bruxelles, Lab Bacteriol Mol, Brussels, Belgium

来源：

NATURE IMMUNOLOGY | 2010年 / 11卷 / 01期

基金：

美国国家卫生研究院;

关键词：

INNATE IMMUNE RECOGNITION; GENOME-WIDE ASSOCIATION; KAPPA-B ACTIVATION; HOST RECOGNITION; CROHN-DISEASE; CELL-DEATH; PEPTIDOGLYCAN; SHIGELLA; LISTERIA; BIOGENESIS;

D O I：

10.1038/ni.1823

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Autophagy is emerging as a crucial defense mechanism against bacteria, but the host intracellular sensors responsible for inducing autophagy in response to bacterial infection remain unknown. Here we demonstrated that the intracellular sensors Nod1 and Nod2 are critical for the autophagic response to invasive bacteria. By a mechanism independent of the adaptor RIP2 and transcription factor NF-kappa B, Nod1 and Nod2 recruited the autophagy protein ATG16L1 to the plasma membrane at the bacterial entry site. In cells homozygous for the Crohn's disease-associated NOD2 frameshift mutation, mutant Nod2 failed to recruit ATG16L1 to the plasma membrane and wrapping of invading bacteria by autophagosomes was impaired. Our results link bacterial sensing by Nod proteins to the induction of autophagy and provide a functional link between Nod2 and ATG16L1, which are encoded by two of the most important genes associated with Crohn's disease.

引用

页码：55 / U67

页数：9

共 47 条

[1] The Crohn's disease protein, NOD2, requires RIP2 in order to induce ubiquitinylation of a novel site on NEMO [J].