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The extracellular matrix protein mindin is a pattern-recognition molecule for microbial pathogens

Nature Immunology volume 5, pages 88–97 (2004)Cite this article

Abstract

Microbial pathogens use a variety of their surface molecules to bind to host extracellular matrix (ECM) components to establish an effective infection. However, ECM components can also serve as an integral part of the innate immunity. Mice lacking expression of mindin (spondin 2), a highly conserved ECM protein, have an impaired ability to clear bacterial infection, and mindin-deficient macrophages show defective responses to a broad spectrum of microbial stimuli. Moreover, mindin binds directly to bacteria and their components and functions as an opsonin for macrophage phagocytosis of bacteria. Thus, mindin is essential in the initiation of the innate immune response and represents a unique pattern-recognition molecule in the ECM for microbial pathogens.

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Figure 1: Characterization of mouse mindin (spondin 2).
Figure 2: Mindin-deficient mice are resistant to LPS-induced septic shock.
Figure 3: Defective responses to various microbial stimuli by mindin-deficient macrophages and mast cells.
Figure 4: Impaired bacterial clearance in the lungs of mindin-deficient mice.
Figure 5: Mindin agglutinates bacteria and binds LPS and LTA.
Figure 6: Mindin functions as an opsonin for macrophage phagocytosis.
Figure 7: Cell signaling in mindin-deficient macrophages stimulated with LPS and TNF.

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Acknowledgements

We thank M. Cook for flow cytometric analysis, and J.R. Wright, L. Hajjar and C.B. Wilson for critically reading this manuscript. This work was supported by National Institutes of Health grant R01 AI54685 (to Y.-W. H.) and the Howard Hughes Medical Institute (to M.J.B.).

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  1. You-Wen He and Hong Li: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Immunology, Duke University Medical Center, Durham, 27710, North Carolina, USA

    You-Wen He, Hong Li, Jun Zhang, Chia-Lin Hsu, Emily Lin, Nu Zhang & Jian Guo

  2. Department of Immunology and Howard Hughes Medical Institute, University of Washington, Seattle, 98195, Washington, USA

    Katherine A Forbush & Michael J Bevan

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He, YW., Li, H., Zhang, J. et al. The extracellular matrix protein mindin is a pattern-recognition molecule for microbial pathogens. Nat Immunol 5, 88–97 (2004). https://doi.org/10.1038/ni1021

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