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Author Notes:

Correspondence to: Richard D. Cummings, Email: rdcummi@emory.edu

Author 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., T.J., R.J.M., and D.F.S., who also helped to perform the experiments and provided critical 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.

We thank Sandy Cummings and Margaret Willard (Emory University) for technical assistance.

We also thank Peng George Wang (Ohio State University) for providing the original E. coli O86:B7 strain, as well as mutant versions of this strain lacking expression of either the Wzy or WaaL genes.

We obtained P. aeruginosa strain 8830 from Dr. Ananda Chakrabaty (University of Illinois College of Medicine) and plasmid pSMC21 encoding GFP from Dr. O'Toole (Dartmouth Medical School), We also thank the staff at the Robert P. Apkarian Integrated Electron Microscopy Core Facility (Emory University) for their help with electron microscopy.

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Research Funding:

This work was supported by grants from the US National of Institutes of Health to R.D.C. (HL085607), 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/U.S. National of Institutes of Health (GM62116).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Biochemistry & Molecular Biology
  • Cell Biology
  • Medicine, Research & Experimental
  • Research & Experimental Medicine
  • HUMAN COLON ECOSYSTEMS
  • ENTERIC BACTERIA
  • GENE-CLUSTER
  • GALECTIN-8
  • RECOGNITION
  • DEGRADATION

Innate immune lectins kill bacteria expressing blood group antigen

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Journal Title:

Nature Medicine

Volume:

Volume 16, Number 3

Publisher:

, Pages 295-U90

Type of Work:

Article | Post-print: After Peer Review

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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© 2010 Nature America, Inc. All rights reserved.

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