Article | Published:

Microbial glycan microarrays define key features of host-microbial interactions

Nature Chemical Biology volume 10, pages 470476 (2014) | Download Citation

Abstract

Genomic approaches continue to provide unprecedented insight into the microbiome, yet host immune interactions with diverse microbiota can be difficult to study. We therefore generated a microbial microarray containing defined antigens isolated from a broad range of microbial flora to examine adaptive and innate immunity. Serological studies with this microarray show that immunoglobulins from multiple mammalian species have unique patterns of reactivity, whereas exposure of animals to distinct microbes induces specific serological recognition. Although adaptive immunity exhibited plasticity toward microbial antigens, immunological tolerance limits reactivity toward self. We discovered that several innate immune galectins show specific recognition of microbes that express self-like antigens, leading to direct killing of a broad range of Gram-negative and Gram-positive microbes. Thus, host protection against microbes seems to represent a balance between adaptive and innate immunity to defend against evolving antigenic determinants while protecting against molecular mimicry.

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Acknowledgements

This work was supported by the US National Blood Foundation and NIH Loan Repayment Grants to S.R.S.; by R01AI050143 and P01HL107151NIH to J.C.P.; by HL085607, P41GM103694 and R24GM098791 to R.D.C.; and by U54GM62116 to the Consortium for Functional Glycomics. S.V.G. was supported by grants from the Swiss National Science Foundation (no. 310030_135734) and from CSL Behring AG, Bern, Switzerland. L.C.R. was supported by grant no. BEX 9320/13-0 from the CAPES Foundation, Ministry of Education, Brazil. We thank T. Ju, X. Song, Y. Wang and S. Cummings for helpful discussion. We also thank L. Robison and J. Rangarajan for help printing the various versions of the MGM. Consortium for Functional Glycomics array data can be accessed at http://www.functionalglycomics.org/.

Author information

Author notes

    • Sean R Stowell
    • , Connie M Arthur
    •  & Ryan McBride

    These authors contributed equally to this work.

Affiliations

  1. Department of Biochemistry and the Glycomics Center, Emory University School of Medicine, Atlanta, Georgia, USA.

    • Sean R Stowell
    • , Connie M Arthur
    • , Jamie Heimburg-Molinaro
    • , Lilian C Rodrigues
    • , Jean-Philippe Gourdine
    • , Alexander J Noll
    • , David F Smith
    •  & Richard D Cummings
  2. Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, USA.

    • Ryan McBride
    • , Oren Berger
    • , Nahid Razi
    •  & James C Paulson
  3. Department of and Chemical Physiology, The Scripps Research Institute, La Jolla, California, USA.

    • Ryan McBride
    • , Oren Berger
    • , Nahid Razi
    •  & James C Paulson
  4. Institute of Pharmacology, University of Bern, Bern, Switzerland.

    • Stephan von Gunten
  5. N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia.

    • Yuriy A Knirel

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Contributions

S.R.S., C.M.A. and R.M. planned the project along with R.D.C. and J.C.P. S.R.S., C.M.A., R.M. and J.H.-M. carried out array experiments and analysis. S.R.S., C.M.A., J.-P.G. and A.J.N. carried out bacterial binding and killing experiments. S.R.S., C.M.A. and L.C.R. carried assays with eukaryotic cells. R.M., O.B., N.R., J.H.-M., S.v.G., D.F.S. and Y.A.K. provided critical bacteria and array reagents and support. S.R.S., C.M.A., J.C.P. and R.D.C. wrote the manuscript, which was additionally edited and commented on by the other authors.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to James C Paulson or Richard D Cummings.

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Results, Supplementary Figures 1–7 and Supplementary Table 1.

Excel files

  1. 1.

    Supplementary Data Set 1

    Raw data obtained on the original version of the microbial glycan microarray (MGMv1).

  2. 2.

    Supplementary Data Set 2

    Raw data obtained on version 4.2 of the Consortium for Functional Glycomics (CFG) mammalian glycan microarray.

  3. 3.

    Supplementary Data Set 3

    Raw data obtained on the expanded version of the microbial glycan microarray (MGM).

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DOI

https://doi.org/10.1038/nchembio.1525

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