The yin yang of bacterial polysaccharides: lessons learned from B. fragilis PSA

Abstract

Over the past several years, there have been remarkable advances in our understanding of how commensal organisms shape host immunity. Although the full cast of immunogenic bacteria and their immunomodulatory molecules remains to be elucidated, lessons learned from the interactions between bacterial zwitterionic polysaccharides (ZPSs) and the host immune system represent an integral step toward better understanding how the intestinal microbiota effect immunologic changes. Somewhat paradoxically, ZPSs, which are found in numerous commensal organisms, are able to elicit both proinflammatory and immunoregulatory responses; both these outcomes involve fine-tuning the balance between T-helper 17 cells and interleukin-10-producing regulatory T cells. In this review, we discuss the immunomodulatory effects of the archetypal ZPS, Bacteroides fragilis PSA. In addition, we highlight some of the opportunities and challenges in applying these lessons in clinical settings.

Fig. 1. Immunomodulatory effects of B. fragilis

The small and large intestines are illustrated. The inset on the left depicts the normal, healthy state with the majority of the microbiota residing in the intestinal lumen and B. fragilis adhering to the mucus layer. Dendritic cells (DCs) sample the luminal content. B. fragilis PSA interacts with TLR2 on DCs and is ultimately presented on the DC surface by MHCII. Naive CD4⁺ T cells recognize MHCII-presented PSA via their T-cell receptor (TCR) and differentiate into IL-10–producing CD4⁺CD25⁺Foxp3⁺ regulatory T cells. The inset on the right depicts a breach of the intestinal barrier (e.g. following surgery or penetrating trauma). Many different bacteria, including B. fragilis, spill into the peritoneal cavity. Th17 cells secrete IL-17 which is essential for abscess formation. Macrophages interact with B. fragilis and secrete IL-10, which is necessary for disease containment.