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Innate immune lectins kill bacteria expressing blood group antigen

Nature Medicine volume 16, pages 295–301 (2010)Cite this article

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Abstract

The expression of ABO(H) blood group antigens causes deletion of cells that generate self-specific antibodies to these antigens but this deletion limits adaptive immunity toward pathogens bearing cognate blood group antigens. To explore potential defense mechanisms against such pathogens, given these limitations in adaptive immunity, we screened for innate proteins that could recognize human blood group antigens. Here we report that two innate immune lectins, galectin-4 (Gal-4) and Gal-8, which are expressed in the intestinal tract, recognize and kill human blood group antigen–expressing Escherichia coli while failing to alter the viability of other E. coli strains or other Gram-negative or Gram-positive organisms both in vitro and in vivo. The killing activity of both Gal-4 and Gal-8 is mediated by their C-terminal domains, occurs rapidly and independently of complement and is accompanied by disruption of membrane integrity. These results demonstrate that innate defense lectins can provide immunity against pathogens that express blood group–like antigens on their surface (pages 263 –264).

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Figure 1: Gal-3, Gal-4 and Gal-8 recognize BGB+ E. coli.
Figure 2: Gal-4 and Gal-8 kill BGB+ E. coli.
Figure 3: Gal-4 and Gal-8 kill BGB+ E. coli solely through the C-terminal domain.
Figure 4: Gal-4 and Gal-8 specifically kill BGB+ E. coli.
Figure 5: Gal-4 and Gal-8 specifically recognize blood group B antigen on BGB+ E. coli.
Figure 6: Gal-4 and Gal-8 specifically kill BGB+ E. coli in vivo.

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Acknowledgements

We thank S. Cummings and M. Willard for technical assistance. We also thank P.G. Wang (Ohio State University) for providing the original E. coli O86:B7 strain, as well as the α-Gal bacteria mutant versions of this strain lacking expression of either the wzy or waaL genes. We obtained P. aeruginosa strain 8830 from A. Chakrabaty (University of Illinois College of Medicine) and plasmid pSMC21 encoding GFP from G. O'Toole (Dartmouth Medical School). We also thank the staff at the Robert P. Apkarian Integrated Electron Microscopy Core Facility at Emory University for their help with electron microscopy. This work was supported by grants from the US National Institutes of Health to R.D.C. (HL085607) and D.F.S. (GM085448) and by resources from the Consortium for Functional Glycomics (Core D and Core H), funded by the US National Institute of General Medical Sciences/US National of Institutes of Health (GM62116).

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  1. Sean R Stowell and Connie M Arthur: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, USA

    Sean R Stowell, Connie M Arthur, Jean-Philippe Gourdine, Jamie Heimburg-Molinaro, Tongzhong Ju, Carlos Rivera-Marrero, Baoyun Xia, David F Smith & Richard D Cummings

  2. Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil

    Marcelo Dias-Baruffi & Lilian C Rodrigues

  3. Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA

    Ross J Molinaro

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Contributions

S.R.S. and C.M.A. planned the project along with R.D.C. and carried out and analyzed the experiments, together with M.D.-B., L.C.R., J.-P.G., J.H.-M., B.X., C.R.-M., T.J., R.J.M. and D.F.S., who also helped to perform the experiments and provided crucial support. S.R.S., C.M.A., J.H.-M. and R.D.C. wrote the manuscript, which was additionally edited and commented on by the other authors.

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Correspondence to Richard D Cummings.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figure 1, Supplementary Table 1 and Supplementary Methods (PDF 1018 kb)

Supplementary Video 1

Immobilization of BGB+ E. coli after addition of Gal-8. BGB+ E. coli observed in real time before and after addition of 5 μM Gal-8 at approximately 20 s. Bacteria show normal movement and viability before addition of galectin and loss of mobility immediately after Gal-8 treatment. (MOV 19257 kb)

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Stowell, S., Arthur, C., Dias-Baruffi, M. et al. Innate immune lectins kill bacteria expressing blood group antigen. Nat Med 16, 295–301 (2010). https://doi.org/10.1038/nm.2103

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