Infection and the Glycome─New Insights into Host Response

Abstract

Glycans play critical roles in the host-pathogen interactions leading to infection. However, we still understand very little about the dynamic nature of glycosylation in response to infection and its function in modulating host immunity. Many of the host proteins involved in immune defense are glycoproteins. Furthermore, the innate immune system recognizes glycans. The glycoform of a protein can impact proteolytic stability, receptor interactions, serum half-life, and other aspects. New, cutting-edge chemical biology tools are shedding light on the interplay between infection and the host glycome. In this review, we highlight new work on the importance of dynamic glycosylation of host proteins in the innate and adaptive immune pathways in response to infection. These include recent findings on altered glycoprofiles of mucins, complement components, and antibodies.

Keywords: adaptive immunity; antibodies; carbohydrates; complement pathway; glycan; glycosylation; host response; innate immunity; macrophages; mucins.

Figure 1

Mucin glycans act as a decoy in host defense. (A) Pathogens bind to the glycan epitopes of secreted and/or cell surface-associated mucins, thereby blocking access to host receptors. (B) The extracellular domains of select cell surface-associated mucins are released upon pathogen binding. Symbolic nomenclature for glycomics (SNFG) is indicated in box.^,

Figure 2

New techniques used in mucin glycobiology. (A) The StcE mucinase cleaves mucins with nonsialylated epitopes. (B) Glycocalyx mimetic microarrays were built using glycopolymers to study influenza A virus.

Figure 3

Complement glycosylation alters in response to infection and immunity. An outline of select aspects of the complement cascade is shown in the center. (A) Proposed mechanism for influenza H1N1 severity and complement activation. High mannose is produced on the cell surface as a result of IRE1 activation during influenza infection. The innate immune lectin MBL2 recognizes high mannose, which leads to complement activation. (B) α-2,6-Sialic acid is enriched in complement components C5 and C9 in severe COVID-19 patients. These components are part of the cascade of events (indicated by arrows) that lead to the formation of the membrane attack complex (MAC). (C) Le^a levels are increased in the C4BP of nonresponders to influenza vaccination. SNFG symbols are shown.

Figure 4

Representation of the single N-glycan site on IgG Fc (Asn297). Common variations in glycosylation are shown. SNFG symbols are shown.