Infection's Sweet Tooth: How Glycans Mediate Infection and Disease Susceptibility

Abstract

Glycans form a highly variable constituent of our mucosal surfaces and profoundly affect our susceptibility to infection and disease. The diversity and importance of these surface glycans can be seen in individuals who lack a functional copy of the fucosyltransferase gene, FUT2. Representing around one-fifth of the population, these individuals have an altered susceptibility to many bacterial and viral infections and diseases. The mediation of host-pathogen interactions by mucosal glycans, such as those added by FUT2, is poorly understood. We highlight, with specific examples, important mechanisms by which host glycans influence infection dynamics, including by: acting as pathogen receptors (or receptor-decoys), promoting microbial stability, altering the physical characteristics of mucus, and acting as immunological markers. We argue that the effect glycans have on infection dynamics has profound implications for many aspects of healthcare and policy, including clinical management, outbreak control, and vaccination policy.

Keywords: FUT2; glycosyltransferase; infection susceptibility; microbiota; viral infection.

Figure 1

α(1,2)-Fucosylated Glycans Affect Infection Susceptibility. (A) Adhering to membrane-bound α(1,2)-fucosylated glycans facilitates pathogen infection. (B) Adhering to luminal α(1,2)-fucosylated glycans can act as a receptor decoy, reducing infection susceptibility. MUC1 glycoprotein is membrane bound, however, detaches from the epithelium following pathogen binding. (C) Commensal microbes can utilise α(1,2)-fucosylated glycans, occupying a niche space and hindering pathogen colonisation. Abbreviations: H. pylori, Helicobacter pylori; C. jejuni, Campylobacter jejuni; S. typhimurium, Salmonella enterica serovar Typhimurium.

Figure 2

Viruses Are Decorated in Host Glycans. Viral replication requires the use of host cell machinery, including host glycosyltransferases. Underlying genetic factors (such as FUT2 SNPs) affect glycosylation of shed viruses. Viral glycoproteins and glycolipids (for enveloped viruses) differ between viruses shed from secretor and nonsecretor cells.