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.

Induction of A. fumigatus-specific CD4-positive T cells in patients recovering from invasive aspergillosis

“…6 In healthy individuals the presence of Aspergillus-specific T cells in peripheral blood was demonstrated by stimulating peripheral blood mononuclear cells (PBMC) with Aspergillus crude extracts or conidia, A. fumigatus recombinant proteins or overlapping peptides of A. fumigatus proteins. 5,[7][8][9][10][11][12][13] We have previously identified Crf1-and Catalase1-specific T cells in healthy individuals using overlapping peptides. Crf1-and Catalase1-specific T cells recognizing a broad variety of T-cell epitopes were identified in the majority of healthy individuals and Aspergillus reactivity was shown by stimulating the T cells with Aspergillus protein extract or recombinant protein.…”

Sphingolipids from the human fungal pathogen Aspergillus fumigatus

“…One of the major GIPC and LGM greatly promote the activation of Th17, and to some degree Th2 responses, in mice and humans. Interestingly, the comparison of LGM and free GM response suggest that IPC lipid anchor enhances a stronger Th17-inducing activity of the glycan moiety [81]. Fungal GlcCer may also interact with the human immune system.…”

“…Purified GIPC and LGM from A. fumigatus mycelium were tested for their capacity to induce immune response after intranasal inoculation to mice or in human T cell culture [81]. One of the major GIPC and LGM greatly promote the activation of Th17, and to some degree Th2 responses, in mice and humans.…”

Immunotherapy for opportunistic infections: Current status and future perspectives

“…71 Later on, the group reported that other proteins such as Pep1, Gel1, Crf1 induced protection against the subsequent Aspergillus infection in similar to the protection by conidia. 72 They found that these antigens can activate human Th1 cells.…”