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An essential role for NOD1 in host recognition of bacterial peptidoglycan containing diaminopimelic acid

Nature Immunology volume 4, pages 702–707 (2003)Cite this article

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Abstract

Nucleotide-binding oligomerization domain protein 1 (NOD1) belongs to a family that includes multiple members with NOD and leucine-rich repeats in vertebrates and plants. NOD1 has been suggested to have a role in innate immune responses, but the mechanism involved remains unknown. Here we report that NOD1 mediates the recognition of peptidoglycan derived primarily from Gram-negative bacteria. Biochemical and functional analyses using highly purified and synthetic compounds indicate that the core structure recognized by NOD1 is a dipeptide, γ-D-glutamyl-meso-diaminopimelic acid (iE-DAP). Murine macrophages deficient in NOD1 did not secrete cytokines in response to synthetic iE-DAP and did not prime the lipopolysaccharide response. Thus, NOD1 mediates selective recognition of bacteria through detection of iE-DAP-containing peptidoglycan.

*Note: In the version of this article initially published online, one author's first name and last name were reversed. The correct author name should be Su Qiu. This mistake has been corrected for the HTML and print versions of the article.

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Figure 1: Recognition of bacterial components by NOD1, NOD2 and TLR4.
Figure 2: The NOD1-stimulatory fraction in the LPS preparation contains DAP-type peptidoglycan.
Figure 3: Peptidoglycan from a subpopulation of bacteria stimulates NOD1.
Figure 4: Stimulation of NOD1 by purified muropeptides and synthetic DMP.
Figure 5: Generation of NOD1-deficient mice.
Figure 6: Absence of cytokine production of Nod1−/− macrophages in response to iE-DAP.

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  • 09 June 2003

    appended aop PDF with corrigendum (will be corrected for print issue), and placed footnote in SGML at abstract

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Acknowledgements

We thank T. Kirikae for stimulating discussions and C. Kirschning, F. Arisaka and A. Hajjar for reagents. This work was supported by grants from the US National Institutes of Health to N.I. and G.N, and from the Canadian Institutes of Health Research to M.A.V. J.M. was supported by funds from Japan Clinical Pathology Foundation for International Exchange and Mochida Memorial Foundation for Medical and Pharmaceutical Research. M.C. was supported by a fellowship from la Fondation pour la Recherche Medicale. Y.O. was supported by a fellowship from Crohn's Colitis Foundation of America. M.A.V. holds a Canada Research Chair in Infectious Diseases and Microbial Pathogenesis.

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Author notes

  1. Mathias Chamaillard, Masahito Hashimoto and Yasuo Horie: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology, The University of Michigan Medical School, Ann Arbor, 48109, Michigan, USA

    Mathias Chamaillard, Junya Masumoto, Su Qiu, Lisa Saab, Yasunori Ogura, Gabriel Nuñez & Naohiro Inohara

  2. Comprehensive Cancer Center, The University of Michigan Medical School, Ann Arbor, 48109, Michigan, USA

    Mathias Chamaillard, Lisa Saab, Yasunori Ogura & Gabriel Nuñez

  3. Department of Infectious Diseases and Tropical Medicine, Research Institute, International Medical Center of Japan, Tokyo, 162-8655, Japan

    Masahito Hashimoto

  4. Ontario Cancer Institute and Department of Medical Biophysics and Immunology, Advanced Medical Discovery Institute, University of Toronto, 620 University Avenue, Toronto, M5G 2C1, Ontario, Canada

    Yasuo Horie & Tak W Mak

  5. Department of Chemistry, Graduate School of Science, Osaka University, Machikaneyama 1-1, Toyonaka, 560-0043, Osaka, Japan

    Akiko Kawasaki, Koichi Fukase & Shoichi Kusumoto

  6. Departments of Microbiology and Immunology, and Medicine, University of Western Ontario, London, N6A 5C1, Ontario, Canada

    Miguel A Valvano

  7. Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, S10 2TN, UK

    Simon J Foster

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Correspondence to Naohiro Inohara.

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Chamaillard, M., Hashimoto, M., Horie, Y. et al. An essential role for NOD1 in host recognition of bacterial peptidoglycan containing diaminopimelic acid. Nat Immunol 4, 702–707 (2003). https://doi.org/10.1038/ni945

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