Campylobacter jejuni and Postinfectious Autoimmune Diseases: A Proof of Concept in Glycobiology

Glycans, one of the most diverse groups of macromolecules, are ubiquitous constituents of all cells and have many critical functions, including the interaction between microbes and their hosts. One of the best model organisms to study the host–pathogen interaction, the gastrointestinal pathogen Campylobacter jejuni dedicates extensive resources to glycosylation and exhibits a diverse array of surface sugar-coated displays. The first bacterium where N-linked glycosylation was described, C. jejuni can additionally modify proteins by O-linked glycosylation, has extracellular capsular polysaccharides that are important for virulence and represent the major determinant of the Penner serotyping scheme, and has outer membrane lipooligosaccharides that participate in processes such as colonization, survival, inflammation, and immune evasion. In addition to causing gastrointestinal disease and extraintestinal infections, C. jejuni was also linked to postinfectious autoimmune neuropathies, of which Guillain–Barré syndrome (GBS) and Miller Fisher syndrome (MFS) are the most extensively characterized ones. These postinfectious autoimmune neuropathies occur when specific bacterial surface lipooligosaccharides mimic gangliosides in the host nervous system. C. jejuni provided the first proof of concept for the involvement of molecular mimicry in the pathogenesis of an autoimmune disease and, also, for the ability of a bacterial polymorphism to shape the clinical presentation of the postinfectious autoimmune neuropathy. The scientific journey that culminated with elucidating the mechanistic details of the C. jejuni–GBS link was the result of contributions from several fields, including microbiology, structural biology, glycobiology, genetics, and immunology and provides an inspiring and important example to interrogate other instances of molecular mimicry and their involvement in autoimmune disease.