The outer surface capsule modulates the binding of Campylobacter jejuni to sialoadhesin-expressing cells

Background: Sialylated lipooligosaccharides (LOS), present in the outer membrane of Campylobacter jejuni, enhance the activation of the innate immune system and are critical for the induction of Guillain-Barré syndrome (GBS). Binding of sialylated LOS to the immune-receptor sialoadhesin leads to bacterial uptake and the release of proinflammatory cytokines by primary human macrophages. However, recent research has indicated that LOS are not always exposed to the external environment. In this study, we determined whether the outer surface capsule shields off the LOS and may prevent the binding of C. jejuni to sialoadhesin.

Methods: Capsule and sialic acid transferase knock-out mutants were generated. Cholera toxin was used to assess the exposure of the LOS to the environment. For sialoadhesin binding experiments, bacteria were FITC- labelled and incubated with sialoadhesin-expressing cells. Cholera toxin and sialoadhesin binding was assessed using flow cytometry.

Results: Cholera toxin binding experiments revealed that the capsule of C. jejuni almost completely shields off the LOS from the environment. This effect was observed for at least three capsular serotypes, HS:1, HS:4 and HS:19. In mutant strains without a capsule, the binding to sialoadhesin was largely enhanced when compared to the encapsulated parental strains. In fact, wild type strains and sialic acid transferase mutants showed comparable low binding to sialoadhesin-expressing cells.

Conclusion: Our results demonstrate that the capsule of C. jejuni can prevent the recognition of C. jejuni by the immune system. Bypassing the capsule to induce a cross-reactive immune response to LOS is a critical step in the pathogenesis of GBS.