Immune sensing of Aspergillus fumigatus proteins, glycolipids, and polysaccharides and the impact on Th immunity and vaccination.
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.
Bozza
Silvia
S
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
Clavaud
Cecile
C
Giovannini
Gloria
G
Fontaine
Thierry
T
Beauvais
Anne
A
Sarfati
Jacqueline
J
D'Angelo
Carmen
C
Perruccio
Katia
K
Bonifazi
Pierluigi
P
Zagarella
Silvia
S
Moretti
Silvia
S
Bistoni
Francesco
F
Latgé
Jean-Paul
JP
Romani
Luigina
L
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*
D000946:Antigens, Fungal; D016207:Cytokines; D005656:Fungal Proteins; D005657:Fungal Vaccines; D006017:Glycolipids; D016056:Immunodominant Epitopes; D011134:Polysaccharides