Full-Length Galectin-3 Is Required for High Affinity Microbial Interactions and Antimicrobial Activity

• Type of Material: Article
• Authors: Shang-Chuen Wu, Harvard Medical School; Alex D Ho, Harvard Medical School; Nourine A Kamili, Emory University; Jianmei Wang, Emory University; Kaleb L Murdock, Harvard Medical School; Richard Cummings, Emory University; Connie Arthur, Emory University; Sean Stowell, Emory University
• Language: English
• Date: 2021-10-08
• Publisher: FRONTIERS MEDIA SA
• Publication Version: Final Published Version
• Copyright Statement: © 2021 Wu, Ho, Kamili, Wang, Murdock, Cummings, Arthur and Stowell.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3389/fmicb.2021.731026
• Title of Journal or Parent Work: FRONTIERS IN MICROBIOLOGY
• Volume: 12
• Start Page: 731026
• End Page: 731026
• Grant/Funding Information: This work was supported in part by the Burroughs Wellcome Trust Career Award for Medical Scientists, the National Institutes of Health Early Independence grant DP5OD019892, and UO1 CA242109 to SS.
• Keywords: Life Sciences & Biomedicine; OLIGOSACCHARIDES; REGULATORS; GLYCAN MICROARRAYS; antimicrobial; BACTERIAL; EPITHELIAL-CELLS; IGE-BINDING PROTEIN; Microbiology; Science & Technology; blood group; CARBOHYDRATE-RECOGNITION DOMAIN; LECTIN; microbe; galectin; LIPOPOLYSACCHARIDES; molecular mimicry; SPECIFICITY
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

While adaptive immunity enables the recognition of a wide range of microbial antigens, immunological tolerance limits reactively toward self to reduce autoimmunity. Some bacteria decorate themselves with self-like antigens as a form of molecular mimicry to limit recognition by adaptive immunity. Recent studies suggest that galectin-4 (Gal-4) and galectin-8 (Gal-8) may provide a unique form of innate immunity against molecular mimicry by specifically targeting microbes that decorate themselves in self-like antigens. However, the binding specificity and antimicrobial activity of many human galectins remain incompletely explored. In this study, we defined the binding specificity of galectin-3 (Gal-3), the first galectin shown to engage microbial glycans. Gal-3 exhibited high binding toward mammalian blood group A, B, and αGal antigens in a glycan microarray format. In the absence of the N-terminal domain, the C-terminal domain of Gal-3 (Gal-3C) alone exhibited a similar overall binding pattern, but failed to display the same level of binding for glycans over a range of concentrations. Similar to the recognition of mammalian glycans, Gal-3 and Gal-3C also specifically engaged distinct microbial glycans isolated and printed in a microarray format, with Gal-3 exhibiting higher binding at lower concentrations toward microbial glycans than Gal-3C. Importantly, Gal-3 and Gal-3C interactions on the microbial microarray accurately predicted actual interactions toward intact microbes, with Gal-3 and Gal-3C displaying carbohydrate-dependent binding toward distinct strains of Providentia alcalifaciens and Klebsiella pneumoniae that express mammalian-like antigens, while failing to recognize similar strains that express unrelated antigens. While both Gal-3 and Gal-3C recognized specific strains of P. alcalifaciens and K. pneumoniae, only Gal-3 was able to exhibit antimicrobial activity even when evaluated at higher concentrations. These results demonstrate that while Gal-3 and Gal-3C specifically engage distinct mammalian and microbial glycans, Gal-3C alone does not possess antimicrobial activity.