The immune receptor NOD1 and kinase RIP2 interact with bacterial peptidoglycan on early endosomes to promote autophagy and inflammatory signaling

Aaron T Irving; Hitomi Mimuro; Thomas A Kufer; Camden Lo; Richard Wheeler; Lorinda J Turner; Belinda J Thomas; Christian Malosse; Michael P Gantier; Linda N Casillas; Bartholomew J Votta; John Bertin; Ivo G Boneca; Chihiro Sasakawa; Dana J Philpott; Richard L Ferrero; Maria Kaparakis-Liaskos

doi:10.1016/j.chom.2014.04.001

The immune receptor NOD1 and kinase RIP2 interact with bacterial peptidoglycan on early endosomes to promote autophagy and inflammatory signaling

Cell Host Microbe. 2014 May 14;15(5):623-35. doi: 10.1016/j.chom.2014.04.001. Epub 2014 Apr 17.

Authors

Aaron T Irving¹, Hitomi Mimuro², Thomas A Kufer³, Camden Lo⁴, Richard Wheeler⁵, Lorinda J Turner⁶, Belinda J Thomas⁷, Christian Malosse⁸, Michael P Gantier¹, Linda N Casillas⁹, Bartholomew J Votta⁹, John Bertin⁹, Ivo G Boneca⁵, Chihiro Sasakawa¹⁰, Dana J Philpott¹¹, Richard L Ferrero⁶, Maria Kaparakis-Liaskos¹²

Affiliations

¹ Centre for Cancer Research, Monash Institute of Medical Research, Clayton, VIC 3168, Australia.
² Division of Bacteriology, Department of Infectious Diseases Control, International Research Center for Infectious Diseases, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
³ Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Köln 50931, Germany.
⁴ Monash Micro Imaging, Clayton, VIC 3168, Australia.
⁵ Institut Pasteur, Unité Biologie et Génétique de la Paroi Bactérienne, Paris 75015, France; INSERM, Avenir group, Paris 75015, France.
⁶ Centre for Innate Immunity and Infectious Diseases, Monash Institute of Medical Research, Clayton, VIC 3168, Australia.
⁷ Centre for Innate Immunity and Infectious Diseases, Monash Institute of Medical Research, Clayton, VIC 3168, Australia; Monash Lung and Sleep, Monash Medical Centre, Clayton, VIC 3168, Australia.
⁸ Institut Pasteur, Structural Mass Spectrometry and Proteomics Unit, Paris 75015, France.
⁹ Pattern Recognition Receptor Discovery Performance Unit, Immuno-Inflammation Therapy Area, GlaxoSmithKline, Collegeville, PA 19426-0989, USA.
¹⁰ Division of Bacterial Infection Biology, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; Nippon Institute for Biological Science, Tokyo 198-0024, Japan; Medical Mycology Research Center, Chiba University, Chiba 260-8673, Japan.
¹¹ Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada.
¹² Centre for Innate Immunity and Infectious Diseases, Monash Institute of Medical Research, Clayton, VIC 3168, Australia. Electronic address: maria.liaskos@monash.edu.

PMID: 24746552
DOI: 10.1016/j.chom.2014.04.001

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Autophagy*
Cell Line
Endosomes / immunology*
Endosomes / microbiology
Helicobacter Infections / enzymology
Helicobacter Infections / genetics
Helicobacter Infections / immunology*
Helicobacter pylori / immunology*
Helicobacter pylori / physiology
Humans
Mice
Nod1 Signaling Adaptor Protein / genetics
Nod1 Signaling Adaptor Protein / immunology*
Peptidoglycan / immunology*
Protein Binding
Pseudomonas Infections / enzymology
Pseudomonas Infections / genetics
Pseudomonas Infections / immunology*
Pseudomonas aeruginosa / immunology*
Pseudomonas aeruginosa / physiology
Receptor-Interacting Protein Serine-Threonine Kinase 2 / genetics
Receptor-Interacting Protein Serine-Threonine Kinase 2 / immunology*
Receptors, Immunologic / genetics
Receptors, Immunologic / immunology*
Signal Transduction

Substances

Nod1 Signaling Adaptor Protein
Peptidoglycan
Receptors, Immunologic
RIPK2 protein, human
Receptor-Interacting Protein Serine-Threonine Kinase 2