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Bacterial membrane vesicles deliver peptidoglycan to NOD1 in epithelial cells

Kaparakis, Maria, Turnbull, Lynne, Carneiro, Leticia, Firth, Stephen, Coleman, Harold A., Parkington, Helena C., Le Bourhis, Lionel, Karrar, Abdulgader, Viala, Jérôme, Mak, Johnson, Hutton, Melanie L., Davies, John K., Crack, Peter J., Hertzog, Paul J., Philpott, Dana, Girardin, Stephen E., Whitchurch, Cynthia B. and Ferrero, Richard L. 2010, Bacterial membrane vesicles deliver peptidoglycan to NOD1 in epithelial cells, Cellular microbiology, vol. 12, no. 3, pp. 372-385, doi: 10.1111/j.1462-5822.2009.01404.x.

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Title Bacterial membrane vesicles deliver peptidoglycan to NOD1 in epithelial cells
Author(s) Kaparakis, Maria
Turnbull, Lynne
Carneiro, Leticia
Firth, Stephen
Coleman, Harold A.
Parkington, Helena C.
Le Bourhis, Lionel
Karrar, Abdulgader
Viala, Jérôme
Mak, JohnsonORCID iD for Mak, Johnson orcid.org/0000-0002-5229-5707
Hutton, Melanie L.
Davies, John K.
Crack, Peter J.
Hertzog, Paul J.
Philpott, Dana
Girardin, Stephen E.
Whitchurch, Cynthia B.
Ferrero, Richard L.
Journal name Cellular microbiology
Volume number 12
Issue number 3
Start page 372
End page 385
Total pages 14
Publisher Wiley - Blackwell Publishing
Place of publication Oxford, England
Publication date 2010-03
ISSN 1462-5814
1462-5822
Keyword(s) animals
epithelial cells
gram-negative bacteria
hela cells
helicobacter pylori
mice
neisseria
NF-kappa B
Nod1 signaling adaptor protein
peptidoglycan
pseudomonas aeruginosa
secretory vesicles
Summary 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.
Language eng
DOI 10.1111/j.1462-5822.2009.01404.x
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2009, Wiley-Blackwell Publishing
Free to Read? Yes
Persistent URL http://hdl.handle.net/10536/DRO/DU:30047433

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
Open Access Collection
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.