title: Induction of innate immunity by Aspergillus fumigatus cell wall polysaccharides is enhanced by the composite presentation of chitin and beta-glucan.
abstract: Chitin and β-glucan are conserved throughout evolution in the fungal cell wall and are the most common polysaccharides in fungal species. Together, these two polysaccharides form a structural scaffold that is essential for the survival of the fungus. In the present study, we demonstrated that Aspergillus fumigatus alkali-insoluble cell wall fragments (AIF), composed of chitin linked covalently to β-glucan, induced enhanced immune responses when compared with individual cell wall polysaccharides. Intranasal administration of AIF induced eosinophil and neutrophil recruitment, chitinase activity, TNF-α and TSLP production in mice lungs. Selective destruction of chitin or β-glucan from AIF significantly reduced eosinophil and neutrophil recruitment as well as chitinase activity and cytokine expression by macrophages, indicating the synergistic effect of the cell wall polysaccharides when presented together as a composite PAMP. We also showed that these cell wall polysaccharides induced chitin-specific IgM in mouse serum. Our in vivo and in vitro data indicate that chitin and β-glucan play important roles in activating innate immunity when presented as composite cell wall PAMPs.
authors.affiliation: Institute of Molecular Medicine, Department of Cardiovascular and Renal Research, University of Southern Denmark, DK-5000 Odense, Denmark.
authors.forename: Lalit Kumar
authors.initials: LK
authors.lastname: Dubey
authors.affiliation: Institute of Molecular Medicine, Department of Cardiovascular and Renal Research, University of Southern Denmark, DK-5000 Odense, Denmark.
authors.forename: Jesper Bonnet
authors.initials: JB
authors.lastname: Moeller
authors.affiliation: Institute of Molecular Medicine, Department of Cardiovascular and Renal Research, University of Southern Denmark, DK-5000 Odense, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Schlosser
authors.affiliation: Institute of Molecular Medicine, Department of Cardiovascular and Renal Research, University of Southern Denmark, DK-5000 Odense, Denmark.
authors.forename: Grith Lykke
authors.initials: GL
authors.lastname: Sorensen
authors.affiliation: Institute of Molecular Medicine, Department of Cardiovascular and Renal Research, University of Southern Denmark, DK-5000 Odense, Denmark. Electronic address: uholmskov@health.sdu.dk.
authors.forename: Uffe
authors.initials: U
authors.lastname: Holmskov
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001228:Aspergillosis / Q000276:immunology*; D001232:Aspergillus fumigatus / Q000276:immunology*; D002465:Cell Movement; D002473:Cell Wall / Q000276:immunology / Q000378:metabolism*; D002686:Chitin / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D002688:Chitinases / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004357:Drug Synergism; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D062610:Fungal Polysaccharides / Q000276:immunology / Q000378:metabolism*; D007113:Immunity, Innate; D008168:Lung / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology*; D051192:Receptors, Pattern Recognition / Q000276:immunology; D047071:beta-Glucans / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*
chemical_list: D016207:Cytokines; D062610:Fungal Polysaccharides; D051192:Receptors, Pattern Recognition; D047071:beta-Glucans; D002686:Chitin; D002688:Chitinases
keywords: A. fumigatus; ABPA; AIF; AMCase; Aspergillus fumigatus; BAL; Chitin; FReD; Fungal cell wall polysaccharides; GlcNAc; Inflammation; Innate immunity; Lung; N-acetylglucosamine; PAMPs; PRRs; acidic mammalian chitinase; alkali-insoluble cell wall fragments; allergic bronchopulmonary aspergillosis; bronchoalveolar lavage; fibrinogen-related domain; pathogen-associated molecular patterns; pattern recognition receptors; β-Glucan