title: Immune sensing of Aspergillus fumigatus proteins, glycolipids, and polysaccharides and the impact on Th immunity and vaccination.
abstract: The ability of the fungus Aspergillus fumigatus to activate, suppress, or subvert host immune response during life cycle in vivo through dynamic changing of cell wall structure and secretion implicates discriminative immune sensing of distinct fungal components. In this study, we have comparatively assessed secreted- and membrane-anchored proteins, glycolipids, and polysaccharides for the ability to induce vaccine-dependent protection in transplanted mice and Th cytokine production by human-specific CD4(+) T cell clones. The results show that the different fungal components are endowed with the distinct capacity to activate Th cell responses in mice and humans, with secreted proteins inducing Th2 cell activation, membrane proteins Th1/Treg, glycolipids Th17, and polysaccharides mostly IL-10 production. Of interest, the side-by-side comparison revealed that at least three fungal components (a protease and two glycosylphosphatidylinositol-anchored proteins) retained their immunodominant Th1/Treg activating potential from mice to humans. This suggests that the broadness and specificity of human T cell repertoire against the fungus could be selectively exploited with defined immunoactive Aspergillus Ags.
authors.affiliation: Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bozza
authors.forename: Cecile
authors.initials: C
authors.lastname: Clavaud
authors.forename: Gloria
authors.initials: G
authors.lastname: Giovannini
authors.forename: Thierry
authors.initials: T
authors.lastname: Fontaine
authors.forename: Anne
authors.initials: A
authors.lastname: Beauvais
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Sarfati
authors.forename: Carmen
authors.initials: C
authors.lastname: D'Angelo
authors.forename: Katia
authors.initials: K
authors.lastname: Perruccio
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Bonifazi
authors.forename: Silvia
authors.initials: S
authors.lastname: Zagarella
authors.forename: Silvia
authors.initials: S
authors.lastname: Moretti
authors.forename: Francesco
authors.initials: F
authors.lastname: Bistoni
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Latgé
authors.forename: Luigina
authors.initials: L
authors.lastname: Romani
mesh_terms: D000818:Animals; D000946:Antigens, Fungal / Q000502:physiology; D001228:Aspergillosis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D001232:Aspergillus fumigatus / Q000276:immunology*; D002999:Clone Cells; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology / Q000382:microbiology / Q000637:transplantation; D005260:Female; D005656:Fungal Proteins / Q000502:physiology*; D005657:Fungal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D006017:Glycolipids / Q000502:physiology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D008172:Lung Diseases, Fungal / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011134:Polysaccharides / Q000502:physiology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*
chemical_list: D000946:Antigens, Fungal; D016207:Cytokines; D005656:Fungal Proteins; D005657:Fungal Vaccines; D006017:Glycolipids; D016056:Immunodominant Epitopes; D011134:Polysaccharides