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

Leonardo H. Travassos, Leticia A.M. Carneiro, Mahendrasingh Ramjeet, Seamus Hussey, Yun Gi Kim, Joo G. Magalhes, Linda Yuan, Fraser Soares, Evelyn Chea, Lionel Le Bourhis, Ivo G. Boneca, Abdelmounaaim Allaoui, Nicola L. Jones, Gabriel Nũez, Stephen E. Girardin, Dana J. Philpott

Research output: Contribution to journalArticlepeer-review

883 Citations (Scopus)

Abstract

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-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.

Original languageEnglish
Pages (from-to)55-62
Number of pages8
JournalNature Immunology
Volume11
Issue number1
DOIs
Publication statusPublished - 2010 Jan 1
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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