Galactosaminogalactan, a New Immunosuppressive Polysaccharide of Aspergillus fumigatus

Abstract

A new polysaccharide secreted by the human opportunistic fungal pathogen Aspergillus fumigatus has been characterized. Carbohydrate analysis using specific chemical degradations, mass spectrometry, 1H and 13C nuclear magnetic resonance showed that this polysaccharide is a linear heterogeneous galactosaminogalactan composed of α1-4 linked galactose and α1-4 linked N-acetylgalactosamine residues where both monosacharides are randomly distributed and where the percentage of galactose per chain varied from 15 to 60%. This polysaccharide is antigenic and is recognized by a majority of the human population irrespectively of the occurrence of an Aspergillus infection. GalNAc oligosaccharides are an essential epitope of the galactosaminogalactan that explains the universal antibody reaction due to cross reactivity with other antigenic molecules containing GalNAc stretches such as the N-glycans of Campylobacter jejuni. The galactosaminogalactan has no protective effect during Aspergillus infections. Most importantly, the polysaccharide promotes fungal development in immunocompetent mice due to its immunosuppressive activity associated with disminished neutrophil infiltrates.

A Polysaccharide Virulence Factor of a Human Fungal Pathogen Induces Neutrophil Apoptosis via NK Cells

“…This percentage of apoptotic PMNs in whole-blood samples increased significantly in the presence of GG, compared with control (mock) solution (Fig. 1A, 1B), as we previously reported (16). The doseresponse relation is shown in Supplemental Fig.…”

“…These toxins are known to inhibit phagocytosis and induce apoptosis of monocytes and neutrophils (60,61). Although GG is a polysaccharide from the cell wall of A. fumigatus, it can be secreted in vivo during early growth and can have an immunosuppressive effect (16). We show in this paper that, in addition to promoting in vivo A. fumigatus growth in a mouse model, GG may also be one of these mycotoxins, through its NK-mediated promotion of PMN apoptosis.…”

“…Polysaccharides from A. fumigatus GG was isolated and purified as described previously (16). Briefly, GG was produced by A. fumigatus (strain CBS 144-89) in a Brian medium 15 l fermentor.…”

“…In addition, the rodlet layer of the conidial surface silences the PMN response (15). We previously showed that galactosaminogalactan (GG), a polysaccharide secreted by the fungus during early growth in vivo, can modulate immune response in a mouse model by increasing PMN apoptosis and favoring A. fumigatus infection (16).…”

Host Cell Invasion by Medically Important Fungi

“…GAG is a heteroglycan composed of variable amounts of galactose and N-acetyl-galactosamine (GalNAc), which is found in the outer layer of the cell wall as well as within the interstitial matrix of fungal biofilms in vitro and in vivo (Loussert et al 2010;Fontaine et al 2011). GAG is produced by hyphae and is not present on conidia (Fontaine et al 2011).…”