Glycoconjugates play a key role in Campylobacter jejuni Infection: interactions between host and pathogen

Abstract

Glycan based interactions between host and pathogen are critical in many bacterial and viral diseases. Glycan interactions range from initial receptor based adherence to protecting the infective agent from the host's immune response through molecular mimicry. Campylobacter jejuni is an ideal model for studying the role of glycans in host-pathogen interactions, as well as the role of bacterial surface glycoconjugates in infection. Using glycan array analysis, C. jejuni has been shown to interact with a wide range of host glycoconjugates. Mannose and sialic acid residues appear to play a role in initial interactions between host and pathogen following environmental exposure, whereas fucose and galactose based interactions are likely to be required for prolonged colonization. Other studies have highlighted potential decoy receptor type interactions between host's intestinal mucins and C. jejuni, demonstrating the importance of host glycoproteins as defense against C. jejuni infection as well as the role for glycoconjugates found in human breast milk in protection of breast feeding infants from infection with C. jejuni. C. jejuni can produce N- and O-linked glycoproteins, capsular polysaccharide (CPS) and/or lipooligosaccharide (LOS) which results in C. jejuni presenting its own diverse sugar coated displays on the cell surface. Bacterial glycans play an important and versatile role in infection and disease. Of these, the best understood is the molecular mimicry of human gangliosides presented by C. jejuni's LOS and its link to the onset of autoimmune neuropathies such as the Guillain Barrè syndrome (GBS). However, the role of glycoconjugates presented by C. jejuni extends beyond expression of sialylated ganglioside structures involved in initiation of GBS. Expression of surface glycans by C. jejuni may also relate to the ability of this organism to interact with the glycoproteins for initial host-pathogen interactions and continued infectivity.

Keywords: LOS; glycans; glycoconjugates.

Figure 1

Campylobacter jejuni and H. pylori host glycoconjugate recognition. H. pylori recognizes lactoceramides and fucosylated structures for the initial contact swapping to sialylated structures during chronic infection. C. jejuni does the opposite recognizing sialic acid and mannose for initial contact and swapping to fucose and galactose after establishing the infection. The proteins involved in H. pylori glycoconjugate recognition are known but in C. jejuni they have yet to be elucidated.

Figure 2

Interactions between bacterial antigens and host immune system. (A) This is the normal process for the interactions between host immune systems and pathogenic bacteria. (1) A portion of the bacterial colony produces different antigens on their surfaces. (2) The immune system targets the surface structures that are presented in a part of the population resulting in other antigens being selected to remain. In this example antibodies are produced to non-sialylated LOS structures. (3) The antigens not targeted by the immune system are allowed to expand causing the infection. (B) This is the model we think is happening for C. jejuni LOS. (1) Each bacterium produces all potential surface antigens in different concentrations. (2) The immune system targets the surface structures that are presented in the population resulting antibody production against a portion of the surface antigens. In this example antibodies are produced to non-sialylated LOS structures. (3) The antigens not targeted by antibodies are still present on the targeted bacteria resulting in the increased likelihood of producing antibodies to those other LOS antigens. If the host has a defect in the mechanisms of ensuring antibodies are not produced against self then C. jejuni producing multiple antigens per bacteria offers a greater risk for the production of anti-self antibodies.