Gut Symbiotic Lipid A Family: Structures and Immunomodulation in IBD
Abstract
As essential molecules composing the outer membrane of gram-negative bacterial pathogens, glycolipids such as lipopolysaccharides (LPSs) and lipooligosaccharides (LOSs) have been extensively investigated, and their shared lipid A structure has been studied in depth. However, studies of the same family of molecules in commensal bacteria are disproportionately scarce. In fact, the LPS/LOS of commensals such as Bacteroides have been regarded as "inactive" in terms of their ability to stimulate host innate pattern recognition receptors (PRRs) and subsequent downstream responses. Recent studies have challenged this poorly documented view, revealing critical contributions of the LPS/LOS of mucosal commensals to host immune development and disease susceptibility. Indeed, commensal lipid A is synthesized with greater structural diversity and more extensive chemical modification than the lipid A of pathogens. However, only a few scattered reports have elucidated the structurefunction relationships of these molecules. We have identified and studied the immunomodulatory capsular polysaccharide A (PSA) of Bacteroides fragilis, a ubiquitous human gut symbiont that signals through Toll-like receptor 2 (TLR2). We have recently found that PSA is covalently attached to a glycolipid anchor (GLA), the structure of which is essentially identical to that of the lipid A of this microbe. Removal of the GLA abrogates the TLR2-mediated immunomodulatory activity of PSA, and much of the innate immune activity of PSA can be recapitulated with the GLA alone. These results led us to hypothesize that structurally diverse lipid A molecules of B. fragilis and related symbiotic bacteria can modulate host immune responses by distinct activation/regulation of PRR-mediated signaling pathways.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2021
- Accession Number
- AD1162352
Entities
People
- Dennis L Kasper
- Sungwhan F. Oh
Organizations
- Harvard Medical School