Bacterial membrane vesicles deliver peptidoglycan to NOD1 in epithelial cells

Kaparakis, M; Turnbull, L; Carneiro, L; Firth, S; Coleman, HA; Parkington, HC; Le Bourhis, L; Karrar, A; Viala, J; Mak, J; Hutton, ML; Davies, JK; Crack, PJ; Hertzog, PJ; Philpott, DJ; Girardin, SE; Whitchurch, CB; Ferrero, RL

Bacterial membrane vesicles deliver peptidoglycan to NOD1 in epithelial cells

Kaparakis, M Turnbull, L

Carneiro, L Firth, S Coleman, HA Parkington, HC Le Bourhis, L Karrar, A Viala, J Mak, J Hutton, ML Davies, JK Crack, PJ Hertzog, PJ Philpott, DJ Girardin, SE Whitchurch, CB

Ferrero, RL

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Publication Type:: Journal Article
Citation:: Cellular Microbiology, 2010, 12 (3), pp. 372 - 385
Issue Date:: 2010-04-15

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Field	Value	Language
dc.contributor.author	Kaparakis, M	en_US
dc.contributor.author	Turnbull, L https://orcid.org/0000-0002-9255-9033	en_US
dc.contributor.author	Carneiro, L	en_US
dc.contributor.author	Firth, S	en_US
dc.contributor.author	Coleman, HA	en_US
dc.contributor.author	Parkington, HC	en_US
dc.contributor.author	Le Bourhis, L	en_US
dc.contributor.author	Karrar, A	en_US
dc.contributor.author	Viala, J	en_US
dc.contributor.author	Mak, J	en_US
dc.contributor.author	Hutton, ML	en_US
dc.contributor.author	Davies, JK	en_US
dc.contributor.author	Crack, PJ	en_US
dc.contributor.author	Hertzog, PJ	en_US
dc.contributor.author	Philpott, DJ	en_US
dc.contributor.author	Girardin, SE	en_US
dc.contributor.author	Whitchurch, CB https://orcid.org/0000-0003-2296-3791	en_US
dc.contributor.author	Ferrero, RL	en_US
dc.date.issued	2010-04-15	en_US
dc.identifier.citation	Cellular Microbiology, 2010, 12 (3), pp. 372 - 385	en_US
dc.identifier.issn	1462-5814	en_US
dc.identifier.uri	http://hdl.handle.net/10453/13769
dc.identifier.uri	http://hdl.handle.net/10453/32976
dc.description.abstract	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. © 2009 Blackwell Publishing Ltd.	en_US
dc.relation.ispartof	Cellular Microbiology	en_US
dc.relation.isbasedon	10.1111/j.1462-5822.2009.01404.x	en_US
dc.subject.classification	Microbiology	en_US
dc.subject.mesh	Hela Cells	en_US
dc.subject.mesh	Secretory Vesicles	en_US
dc.subject.mesh	Epithelial Cells	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Gram-Negative Bacteria	en_US
dc.subject.mesh	Neisseria	en_US
dc.subject.mesh	Pseudomonas aeruginosa	en_US
dc.subject.mesh	Helicobacter pylori	en_US
dc.subject.mesh	Peptidoglycan	en_US
dc.subject.mesh	NF-kappa B	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Male	en_US
dc.subject.mesh	Nod1 Signaling Adaptor Protein	en_US
dc.subject.mesh	HeLa Cells	en_US
dc.title	Bacterial membrane vesicles deliver peptidoglycan to NOD1 in epithelial cells	en_US
dc.type	Journal Article
utslib.citation.volume	3	en_US
utslib.citation.volume	12	en_US
utslib.for	0605 Microbiology	en_US
utslib.for	1108 Medical Microbiology	en_US
dc.location.activity	Melbourne, Australia
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - ithree - Institute of Infection, Immunity and Innovation
utslib.copyright.status	open_access
pubs.issue	3	en_US
pubs.publication-status	Published	en_US
pubs.volume	12	en_US

Abstract:

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. © 2009 Blackwell Publishing Ltd.

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http://hdl.handle.net/10453/13769