Abstract
Epithelial cells can respond to conserved bacterial products that are internalized after either bacterial invasion or liposome treatment of cells. We report here that the noninvasive Gram-negative pathogen Helicobacter pylori was recognized by epithelial cells via Nod1, an intracellular pathogen-recognition molecule with specificity for Gram-negative peptidoglycan. Nod1 detection of H. pylori depended on the delivery of peptidoglycan to host cells by a bacterial type IV secretion system, encoded by the H. pylori cag pathogenicity island. Consistent with involvement of Nod1 in host defense, Nod1-deficient mice were more susceptible to infection by cag pathogenicity island–positive H. pylori than were wild-type mice. We propose that sensing of H. pylori by Nod1 represents a model for host recognition of noninvasive pathogens.
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Acknowledgements
We thank D. Blanot for the LysA assays; S. Saurin and M. Tanguy for histological analyses; R. Peek for the H. pylori B128 strain; L. Bougneres for advice regarding tyrosine phosphorylation assays; members of Programme Transversal de Recherche (PTR) project 94 for sharing information and materials; and L. Ferrero for reading of the manuscript. J.B., D.J.P. and R.L.F. share senior authorship. Supported by the Institut Pasteur (PTR94; S.E.G., D.J.P. and R.L.F.); Health Research Board of Ireland (A.P.M.); Laboratoires Sanofi-Synthélabo, La Société des Eaux Minérales d'Evian and INSERM (J.V.); the French Ministry of Science (C.C.); the Fundação para a Ciência e a Tecnologia of Portugal (I.G.B.); and Danone Vitapole (S.E.G.). P.J.S. is a Howard Hughes International Research Scholar.
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Supplementary information
Supplementary Fig. 1
Absence of cagA and cagF. gene homologues in H. felis by Southern hybridization. (PDF 61 kb)
Supplementary Fig. 2
A mutation in the slt gene does not affect the H. pylori type IV secretion apparatus. (PDF 94 kb)
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Viala, J., Chaput, C., Boneca, I. et al. Nod1 responds to peptidoglycan delivered by the Helicobacter pylori cag pathogenicity island. Nat Immunol 5, 1166–1174 (2004). https://doi.org/10.1038/ni1131
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DOI: https://doi.org/10.1038/ni1131
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