Lipopolysaccharide associated with 13-2,6 fructan mediates TLR4-dependent immunomodulatory activity in vitro

Levan, a 13-2,6 fructofuranose polymer produced by microbial species, has been reported for its immunomodu-latory properties via interaction with toll-like receptor 4 (TLR4) which recognises lipopolysaccharide (LPS). However, the molecular mechanisms underlying these interactions remain elusive. Here, we investigated the immunomodulatory properties of levan using thoroughly-purified and characterised samples from Erwinia her-bicola and other sources. E. herbicola levan was purified by gel-permeation chromatography and LPS was removed from the levan following a novel alkali treatment developed in this study. E. herbicola levan was then characterised by gas chromatography-mass spectrometry and NMR. We found that levan containing LPS, but not LPS-depleted levan, induced TLR4-mediated cytokine production by bone marrow-derived dendritic cells and/or activated TLR4 reporter cells. These data indicated that the immunomodulatory properties of the levan toward TLR4-expressing immune cells were mediated by the LPS. This work also demonstrates the importance of LPS removal when assessing the immunomodulatory activity of polysaccharides.

Automated summary

This study investigates the immunomodulatory properties of Levan and finds that its interaction with TLR4 through LPS mediates the immune response in immune cells.