Galectin-9 recognizes and exhibits antimicrobial activity toward microbes expressing blood group-like antigens

• Type of Material: Article
• Authors: Anna Blenda, Emory University; Nourine A Kamili, Emory University School of Medicine; Shang-Chuen Wu, Harvard Medical School; William F Abel, University of South Carolina School of Medicine Greenville; Diyoly Ayona, Harvard Medical School; Christian Gerner-Smidt, Emory University School of Medicine; Alex D Ho, Harvard Medical School; Guy Benian, Emory University; Richard Cummings, Emory University; Connie Arthur, Emory University; Sean Stowell, Emory University
• Language: English
• Date: 2022-04-01
• Publisher: Emory University Libraries
• Publication Version: Final Published Version
• Copyright Statement: © 2022 The Authors
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.jbc.2022.101704
• Title of Journal or Parent Work: Journal of Biological Chemistry
• Volume: 298
• Issue: 4
• Start Page: 101704
• End Page: 101704
• Grant/Funding Information: This work was primarily supported by the Burroughs Wellcome Trust CAMS award and the National Institutes of Health (grant nos.: DP5OD019892 and U01CA242109) awards to S. R. S. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
• Keywords: glycan array; carbohydrate-binding protein; Mammals; Anti-Infective Agents; Polysaccharides; antimicrobial; galectin-9; Animals; Galectins; blood group antigen; Blood Group Antigens
• Research Categories: Health Sciences, Pathology; Health Sciences, Medicine and Surgery

Abstract

While adaptive immunity recognizes a nearly infinite range of antigenic determinants, immune tolerance renders adaptive immunity vulnerable to microbes decorated in self-like antigens. Recent studies suggest that sugar-binding proteins galectin-4 and galectin-8 bind microbes expressing blood group antigens. However, the binding profile and potential antimicrobial activity of other galectins, particularly galectin-9 (Gal-9), has remained incompletely defined. Here, we demonstrate that while Gal-9 possesses strong binding preference for ABO(H) blood group antigens, each domain exhibits distinct binding patterns, with the C-terminal domain (Gal-9C) exhibiting higher binding to blood group B than the N-terminal domain (Gal-9N). Despite this binding preference, Gal-9 readily killed blood group B-positive Escherichia coli, whereas Gal-9N displayed higher killing activity against this microbe than Gal-9C. Utilization of microarrays populated with blood group O antigens from a diverse array of microbes revealed that Gal-9 can bind various microbial glycans, whereas Gal-9N and Gal-9C displayed distinct and overlapping binding preferences. Flow cytometric examination of intact microbes corroborated the microbial glycan microarray findings, demonstrating that Gal-9, Gal-9N, and Gal-9C also possess the capacity to recognize distinct strains of Providencia alcalifaciens and Klebsiella pneumoniae that express mammalian blood group-like antigens while failing to bind related strains that do not express mammalian-like glycans. In each case of microbial binding, Gal-9, Gal-9N, and Gal-9C induced microbial death. In contrast, while Gal-9, Gal-9N, and Gal-9C engaged red blood cells, each failed to induce hemolysis. These data suggest that Gal-9 recognition of distinct microbial strains may provide antimicrobial activity against molecular mimicry.