Definition of the Anti-inflammatory Oligosaccharides Derived From the Galactosaminogalactan (GAG) From Aspergillus fumigatus

• Main Authors: Markus Gressler, Christoph Heddergott, Inés C. N'Go, Giorgia Renga, Vasilis Oikonomou, Silvia Moretti, Bernadette Coddeville, Joana Gaifem, Ricardo Silvestre, Luigina Romani, Jean-Paul Latgé, Thierry Fontaine
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2019-11-01
• Series: Frontiers in Cellular and Infection Microbiology
• Subjects: galactosaminogalactan; Aspergillus fumigatus; IL-Ra; anti-inflammatory response; glycodrug
• Online Access: https://www.frontiersin.org/article/10.3389/fcimb.2019.00365/full

Galactosaminogalactan (GAG) is an insoluble aminosugar polymer produced by Aspergillus fumigatus and has anti-inflammatory properties. Here, the minimum glycosidic sequences required for the induction of IL-1Ra by peripheral blood mononuclear cells (PBMCs) was investigated. Using chemical degradation of native GAG to isolate soluble oligomers, we have found that the de-N-acetylation of galactosamine residues and the size of oligomer are critical for the in vitro immune response. A minimal oligomer size of 20 galactosamine residues is required for the anti-inflammatory response but the presence of galactose residues is not necessary. In a Dextran sulfate induced colitis mouse model, a fraction of de-N-acetylated oligomers of 13 < dp < 20 rescue inflammatory damage like the native GAG polymer in an IL-1Ra dependent pathway. Our results demonstrate the therapeutic suitability of water-soluble GAG oligosaccharides in IL-1 mediated hyper-inflammatory diseases and suggest that α-1,4-galactosamine oligomers chemically synthesized could represent new anti-inflammatory glycodrugs.