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Bacterial membrane vesicles deliver peptidoglycan to NOD1 in epithelial cells

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journal contribution
posted on 2010-03-01, 00:00 authored by M Kaparakis, L Turnbull, L Carneiro, Stephen Firth, H Coleman, H Parkington, L Le Bourhis, A Karrar, J Viala, Johnson Mak, M Hutton, J Davies, P Crack, P Hertzog, D Philpott, S Girardin, C Whitchurch, R Ferrero
Gram-negative bacterial peptidoglycan is specifically recognized by the host intracellular sensor NOD1, resulting in the generation of innate immune responses. Although epithelial cells are normally refractory to external stimulation with peptidoglycan, these cells have been shown to respond in a NOD1-dependent manner to Gram-negative pathogens that can either invade or secrete factors into host cells. In the present work, we report that Gram-negative bacteria can deliver peptidoglycan to cytosolic NOD1 in host cells via a novel mechanism involving outer membrane vesicles (OMVs). We purified OMVs from the Gram-negative mucosal pathogens: Helicobacter pylori, Pseudomonas aeruginosa and Neisseria gonorrhoea and demonstrated that these peptidoglycan containing OMVs upregulated NF-κB and NOD1-dependent responses in vitro. These OMVs entered epithelial cells through lipid rafts thereby inducing NOD1-dependent responses in vitro. Moreover, OMVs delivered intragastrically to mice-induced innate and adaptive immune responses via a NOD1-dependent but TLR-independent mechanism. Collectively, our findings identify OMVs as a generalized mechanism whereby Gram-negative bacteria deliver peptidoglycan to cytosolic NOD1. We propose that OMVs released by bacteria in vivo may promote inflammation and pathology in infected hosts.

History

Journal

Cellular microbiology

Volume

12

Issue

3

Pagination

372 - 385

Publisher

Wiley - Blackwell Publishing

Location

Oxford, England

ISSN

1462-5814

eISSN

1462-5822

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal

Copyright notice

2009, Wiley-Blackwell Publishing