The Host Glycome in Health and Immunity

Abstract

Glycosylation is the enzymatic modification of biomacromolecules (proteins, etc.) with carbohydrates known as glycans. Naturally occurring in all organisms from viruses to animals, glycans have multifaceted functions in all aspects of biology. Aberrant glycosylation is often observed in diseases such as cancers and in developmental abnormalities. In infectious disease, studies have heavily focused on the glycans of the pathogens, which can determine the immunogenicity and virulence of the pathogens. The less studied host glycans are also critical in immunity, influencing antibody function, complement system activation, and modulate immune cell functions. Due to the structural diversity of glycans, pinpointing the host glycan subtypes that undergo changes during infections can be a challenging task. In the original work described in this thesis, high-throughput lectin microarray technology was utilized to profile the glycomes related to human health and infection (i.e., the repertoires of glycans) in multiple systems. Glycomic analyses revealed differential glycosylation in the contexts of (i) sex, age, BMI, (ii) Coronavirus disease 2019 (COVID-19) and (iii) vaccination, which are associated with immune response or disease outcome. Moreover, glycoproteomic analyses identified potential target glycoproteins that may contribute to the differences in glycosylation and immunity. Overall, these discoveries provide fresh insights into the roles of host glycans in infectious diseases and have important implications in the development of glycosylation-focused therapeutics.